</head> <body>Wang et al. (2002) have shown that EGFR signalling from endosomes leads to cell survival. PMID: 19615955</body> </html> </notes> <label text="Late Endosomes"> <bbox w="75.0" h="10.0" x="870.5" y="929.5"/> </label> <bbox w="704.0" h="534.0" x="886.0" y="2197.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="118.0" y="1884.5"/> </label> <bbox w="4114.0" h="590.0" x="109.0" y="2844.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <label text="Golgi Apparatus"> <bbox w="80.0" h="10.0" x="135.0" y="844.5"/> </label> <bbox w="423.0" h="557.0" x="150.0" y="2106.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c6_mpk1_mpk1_ca6"> <label text="Endoplasmic Reticulum"> <bbox w="110.0" h="10.0" x="112.0" y="661.5"/> </label> <bbox w="195.0" h="120.0" x="147.0" y="1926.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c7_mpk1_mpk1_ca7"> <label text="Mitochondria"> <bbox w="65.0" h="10.0" x="1341.0" y="589.5"/> </label> <bbox w="360.0" h="300.0" x="1117.0" y="1847.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <label text="Early Endosomes"> <bbox w="80.0" h="10.0" x="2048.5" y="793.5"/> </label> <bbox w="666.0" h="215.0" x="2066.0" y="2056.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" x="85.5" y="565.5"/> </label> <bbox w="4170.0" h="1745.0" x="84.0" y="1780.0"/> </glyph> <glyph class="compartment" id="mpk1_mpk1_c11_mpk1_mpk1_ca11"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="141.5" y="2267.5"/> </label> <bbox w="4232.0" h="2304.0" x="60.0" y="1280.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c2_akt1_akt1_ca2"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="703.5" y="1428.0"/> </label> <bbox w="614.0" h="485.0" x="4885.0" y="1029.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c6_akt1_akt1_ca6"> <label text="Endosome"> <bbox w="45.0" h="10.0" x="2233.0" y="562.5"/> </label> <bbox w="335.0" h="502.0" x="6469.0" y="139.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c7_akt1_akt1_ca7"> <label text="Lipid Raft"> <bbox w="55.0" h="10.0" x="1264.5" y="512.5"/> </label> <bbox w="1272.0" h="477.0" x="4650.0" y="121.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c3_akt1_akt1_ca3"> <label text="Endosome Membrane"> <bbox w="90.0" h="10.0" x="1825.5" y="1378.5"/> </label> <bbox w="689.0" h="339.0" x="6005.0" y="1138.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c5_akt1_akt1_ca5"> <label text="Mitochondria"> <bbox w="65.0" h="10.0" x="2176.5" y="690.5"/> </label> <bbox w="399.0" h="452.0" x="6396.0" y="678.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c1_akt1_akt1_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" x="967.5" y="878.0"/> </label> <bbox w="2496.0" h="2445.0" x="4384.0" y="93.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c4_akt1_akt1_ca4" compartmentRef="akt1_akt1_c1_akt1_akt1_ca1"> <label text="Membrane Lysosome"> <bbox w="90.0" h="10.0" x="2014.0" y="2122.5"/> </label> <bbox w="1015.0" h="693.0" x="5816.0" y="1561.0"/> </glyph> <glyph class="compartment" id="akt1_akt1_c8_akt1_akt1_ca8"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="878.0" y="52.5"/> </label> <bbox w="2500.0" h="2500.0" x="4382.0" y="40.0"/> </glyph> <glyph class="compartment" id="akt1_akt2_c2_akt1_akt2_ca2"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="1120.5" y="2915.5"/> </label> <bbox w="1981.0" h="1703.0" x="4655.0" y="2903.0"/> </glyph> <glyph class="compartment" id="akt1_akt2_c1_akt1_akt2_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" x="1322.5" y="2635.5"/> </label> <bbox w="2499.0" h="2454.0" x="4382.0" y="2623.0"/> </glyph> <glyph class="compartment" id="akt1_akt2_c3_akt1_akt2_ca3"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="755.0" y="2592.5"/> </label> <bbox w="2500.0" h="2500.0" x="4382.0" y="2580.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc1_c2_wnc1_wnc1_ca2"> <label 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compartmentRef="wnc1_wnc1_c1_wnc1_wnc1_ca1"> <label text="Endoplasmic Reticulum"> <bbox w="110.0" h="10.0" x="513.5" y="961.5"/> </label> <bbox w="350.0" h="144.0" x="7292.0" y="949.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc1_c3_wnc1_wnc1_ca5" compartmentRef="wnc1_wnc1_c1_wnc1_wnc1_ca1"> <label text="Endoplasmic Reticulum"> <bbox w="110.0" h="10.0" x="1061.0" y="1182.5"/> </label> <bbox w="236.0" h="190.0" x="8008.0" y="1109.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc1_c8_wnc1_wnc1_ca10"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="77.0" y="92.5"/> </label> <bbox w="2650.0" h="2700.0" x="7012.0" y="80.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc2_c4_wnc1_wnc2_ca4"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="3801.0" y="1914.5"/> </label> <bbox w="1005.0" h="567.0" x="10704.0" y="1664.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc2_c3_wnc1_wnc2_ca3"> <label text="Mitochondria"> <bbox w="65.0" h="10.0" x="2967.5" y="1216.5"/> </label> <bbox w="625.0" h="318.0" x="9885.0" y="1204.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc2_c1_wnc1_wnc2_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" x="2910.5" y="832.5"/> </label> <bbox w="2081.0" h="2202.0" x="9821.0" y="451.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc2_c5_wnc1_wnc2_ca5"> <label text="Neighbouring Cell"> <bbox w="90.0" h="10.0" x="4270.5" y="297.5"/> </label> <bbox w="739.0" h="75.0" x="11202.0" y="285.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc2_c6_wnc1_wnc2_ca6"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="2753.0" y="292.5"/> </label> <bbox w="2500.0" h="2500.0" x="9688.0" y="280.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc3_c2_wnc1_wnc3_ca2"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="1256.0" y="3143.5"/> </label> <bbox w="1773.0" h="1823.0" x="7555.0" y="3131.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc3_c1_wnc1_wnc3_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" 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compartmentRef="wnc1_wnc4_c1_wnc1_wnc4_ca1"> <label text="Mitochondria"> <bbox w="65.0" h="10.0" x="3782.5" y="3570.5"/> </label> <bbox w="393.0" h="343.0" x="10700.0" y="3558.0"/> </glyph> <glyph class="compartment" id="wnc1_wnc4_c5_wnc1_wnc4_ca5"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="2753.0" y="2808.5"/> </label> <bbox w="2500.0" h="2500.0" x="9688.0" y="2796.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c1_wca1_wca1_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" x="777.5" y="2609.5"/> </label> <bbox w="2734.0" h="2669.0" x="12343.0" y="216.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c2_wca1_wca1_ca2"> <label text="Cilium"> <bbox w="35.0" h="10.0" x="807.0" y="191.5"/> </label> <bbox w="276.0" h="213.0" x="13022.0" y="65.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c3_wca1_wca1_ca3" compartmentRef="wca1_wca1_c1_wca1_wca1_ca1"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="727.5" y="1258.5"/> </label> <bbox w="223.0" h="210.0" x="12906.5" y="1135.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c5_wca1_wca1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Endosome"> <bbox w="45.0" h="10.0" x="1953.0" y="1286.5"/> </label> <bbox w="1053.0" h="764.0" x="13818.0" y="609.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c5_wca1_wca1_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Endosome"> <bbox w="45.0" h="10.0" x="1954.0" y="2221.5"/> </label> <bbox w="1131.0" h="756.0" x="13803.0" y="1552.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c5_wca1_wca1_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Endosome"> <bbox w="45.0" h="10.0" x="1695.5" y="2518.5"/> </label> <bbox w="785.0" h="339.0" x="13772.0" y="2324.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c5_wca1_wca1_ca8"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Endosome"> <bbox w="45.0" h="10.0" x="2321.5" y="2519.5"/> </label> <bbox w="233.0" h="209.0" x="14574.0" y="2397.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c5_wca1_wca1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Endosome"> <bbox w="45.0" h="10.0" x="2557.5" y="2515.5"/> </label> <bbox w="97.0" h="207.0" x="14844.0" y="2399.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c4_wca1_wca1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Vaceolae"> <bbox w="45.0" h="10.0" x="1278.5" y="351.5"/> </label> <bbox w="1515.0" h="369.0" x="13545.0" y="84.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c6_wca1_wca1_ca10" compartmentRef="wca1_wca1_c1_wca1_wca1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Multivesicular bodies are required to sequester away GSK3, Axin from newly synthesised b-catenin. 21183076</body> </html> </notes> <label text="Multivesicular Body"> <bbox w="100.0" h="10.0" x="1808.5" y="2607.5"/> </label> <bbox w="1209.0" h="1198.0" x="13757.0" y="1496.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c7_wca1_wca1_ca11"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="54.0" y="62.5"/> </label> <bbox w="3000.0" h="3000.0" x="12338.0" y="50.0"/> </glyph> <glyph class="compartment" id="wca1_wca2_c2_wca1_wca2_ca2"> <label text="Endosome"> <bbox w="45.0" h="10.0" x="3821.5" y="951.5"/> </label> <bbox w="292.0" h="168.0" x="16108.0" y="939.0"/> </glyph> <glyph class="compartment" id="wca1_wca2_c2_wca1_wca2_ca3"> <label text="Endosome"> <bbox w="45.0" h="10.0" x="3649.5" y="1341.5"/> </label> <bbox w="899.0" h="322.0" x="15936.0" y="1329.0"/> </glyph> <glyph class="compartment" id="wca1_wca2_c3_wca1_wca2_ca4"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="3667.0" y="1811.5"/> </label> <bbox w="460.0" h="174.0" x="15946.0" y="1799.0"/> </glyph> <glyph class="compartment" id="wca1_wca2_c1_wca1_wca2_ca1"> <label text="Cytoplasm"> <bbox w="50.0" h="10.0" x="3242.5" y="2463.5"/> </label> <bbox w="2167.0" h="2273.0" x="15529.0" y="777.0"/> </glyph> <glyph class="compartment" id="wca1_wca2_c5_wca1_wca2_ca6"> <label text="Extracellular space"> <bbox w="100.0" h="10.0" x="3059.0" y="562.5"/> </label> <bbox w="2500.0" h="2500.0" x="15370.0" y="550.0"/> </glyph> <glyph class="compartment" id="wca1_wca2_c4_wca1_wca2_ca5" compartmentRef="wca1_wca2_c1_wca1_wca2_ca1"> <label text="Early Endosome"> <bbox w="75.0" h="10.0" x="5101.5" y="1985.5"/> </label> <bbox w="164.0" h="133.0" x="17404.0" y="1973.0"/> </glyph> <glyph class="compartment" id="wca1_wca3_c2_wca1_wca3_ca2"> <label text="Nucleus"> <bbox w="40.0" h="10.0" x="1278.0" y="3598.5"/> </label> <bbox w="2008.0" h="1744.0" x="13139.0" y="3586.0"/> </glyph> <glyph class="compartment" 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x="432.5" y="2442.5"/> </label> <bbox w="2470.0" h="2392.0" x="17952.0" y="156.0"/> </glyph> <glyph class="compartment" id="shh1_shh2_c1_shh1_shh2_ca1"> <label text="Cytosol"> <bbox w="40.0" h="10.0" x="1230.5" y="2667.5"/> </label> <bbox w="2489.0" h="2197.0" x="17951.0" y="2655.0"/> </glyph> <glyph class="compartment" id="shh1_shh2_c1_shh1_shh3_ca1"> <label text="Cytosol"> <bbox w="40.0" h="10.0" x="1257.5" y="4979.5"/> </label> <bbox w="2400.0" h="857.0" x="17981.0" y="4959.0"/> </glyph> <glyph class="macromolecule" id="gf1_s14_gf1_sa30" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PDGFA HUGO:PDGFB HUGO:PDGFC HUGO:PDGFD MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23123598 PDGF stimulation of CAFs induces production of the prototypical pro-angiogenic inducer fibroblast growth factor (FGF)-2 in both cervical carcinomas and melanoma [11] and [85]. Interestingly, CAFs activated by PDGF-CC in melanomas also secrete the extracellular matrix protein osteopontin, the action of which is known to synergistically stimulate angiogenesis together with FGF-2 and promote autocrine VEGF-A signaling in endothelial cells PMID:15207817; PMID:19118022 PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Tumor fibroblasts a recruted by PDGF PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR?? and ??, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells</body> </html> </notes> <label text="PDGF*"/> <bbox w="80.0" h="40.0" x="273.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4526_gf1_sa32" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGF1 HUGO:FGF2 HUGO:FGF3 HUGO:FGF4 HUGO:FGF5 HUGO:FGF6 HUGO:FGF7 HUGO:FGF8 HUGO:FGF9 HUGO:FGF10 HUGO:FGF11 HUGO:FGF12 HUGO:FGF13 HUGO:FGF14 HUGO:FGF16 HUGO:FGF17 HUGO:FGF18 HUGO:FGF19 HUGO:FGF20 HUGO:FGF21 HUGO:FGF22 HUGO:FGF23 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Deregulation of FGF signaling pathways have been implicated in many types of human and animal cancers.</body> </html> </notes> <label text="FGF*"/> <bbox w="80.0" h="40.0" x="612.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s423_gf1_sa35" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PGDFRA HUGO:PGDFRB MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR alpha and beta, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGFRA binds to all PDGF isoforms except PDGF-DD, while PDGFRB is activated by PDGF-BB and -DD. PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells . The large protein complex recruited by phosphorylated PDGF receptors is seen as a dynamic signalosome that controls cell fate.</body> </html> </notes> <label text="PDGFR*"/> <bbox w="80.0" h="50.0" x="402.5" y="322.5"/> <glyph class="unit of information" id="_cfb9f562-7303-40b5-9d22-98a3b1098d92"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="420.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4554_gf1_sa37" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:FRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Downstream of the signaling tyrosine kinase FGFRs, intracellular signaling cascades are also tightly regulated by specialized adaptor proteins such as FGFR substrate 2?? (FRS2??) and regulators of the RAS???MAPK and PI3K???AKT pathways such as Sprouty (SPRY) proteins Identifiers_begin: fibroblast growth factor receptor substrate 2 HUGO:FRS2 HGNC:16971 ENTREZ:10818 UNIPROT:Q8WU20 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="FRS2"/> <bbox w="80.0" h="40.0" x="743.5" y="777.5"/> <glyph class="state variable" id="_88f497f6-47b9-45d5-a401-96eed3e320e7"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="736.0" y="792.5"/> </glyph> <glyph class="state variable" id="_e6cf9f56-a9ee-4c5a-a77e-20d0e7b8a961"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="738.5" y="792.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4547_gf1_sa38" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:FRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Downstream of the signaling tyrosine kinase FGFRs, intracellular signaling cascades are also tightly regulated by specialized adaptor proteins such as FGFR substrate 2?? (FRS2??) and regulators of the RAS???MAPK and PI3K???AKT pathways such as Sprouty (SPRY) proteins Identifiers_begin: fibroblast growth factor receptor substrate 2 HUGO:FRS2 HGNC:16971 ENTREZ:10818 UNIPROT:Q8WU20 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="FRS2"/> <bbox w="80.0" h="40.0" x="742.5" y="667.5"/> <glyph class="state variable" id="_6586a8f8-b596-4528-97c5-f6b65d3b40f2"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="737.5" y="682.5"/> </glyph> <glyph class="state variable" id="_a313650d-c386-43d5-a1ec-9de79ba78ea5"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="737.5" y="682.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4735_gf1_sa42" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGFR1 HUGO:FGFR2 HUGO:FGFR3 HUGO:FGFR4 HUGO:FGFRL1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25467007 FGFRs _rew PMID:25772309 Binding of canonical FGFs to FGFR with HS (or HSPG) as a cofactor induces the formation of ternary FGF???FGFR???HS complex, which activates the FGFR intracellular tyrosine kinase domain by phosphorylation of specific tyrosine residues. The activated receptor is coupled to intracellular signaling pathways including the RAS???MAPK, PI3K???AKT, PLC??, and STAT pathways.</body> </html> </notes> <label text="FGFR*"/> <bbox w="80.0" h="50.0" x="722.5" y="322.5"/> <glyph class="unit of information" id="_5aaf00f0-642b-4d22-a4a7-f19e613fdf9c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="740.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4506_gf1_sa44" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:AREG MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="AREG"/> <bbox w="80.0" h="40.0" x="1192.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s416_gf1_sa45" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:ERBB2 HUGO:ERBB3 HUGO:ERBB4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40).</body> </html> </notes> <label text="ERBB*"/> <bbox w="80.0" h="50.0" x="1522.5" y="322.5"/> <glyph class="unit of information" id="_9ff62a8a-d756-4279-a344-4a8fffd382c7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1540.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s102_gf1_sa46" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:EGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="EGF"/> <bbox w="80.0" h="40.0" x="1482.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s415_gf1_sa48" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:EGFR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40). PMID:28513565 Epidermal growth factor receptor (EGFR) signaling pathways leading to G1/S cell cycle progression activated by EGF activation. Depicted are the RAS-RAF-MEK-ERK MAPK and PI3K-AKT-mTOR pathways. Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)", ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="EGFR"/> <bbox w="80.0" h="50.0" x="1462.5" y="432.5"/> <glyph class="unit of information" id="_d604d9b7-31e5-42b4-af5d-33543525e60f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1480.0" y="427.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4593_gf1_sa52" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2R MODULE:GROWTH_FACTORS_SIGNALING_PATHWAYS PMID:27548915 One function of IGF2R is to bind to the ligand IGF2, leading to IGF2 degradation and consequently an inhibition of the growth stimulation that results from the interaction between IGF2 and IGF1R48, 49. IGF2 is upregulated in CAFs50, suggesting that IGF2R is inhibited. Therefore, reduction in IGF2R following treatment with miR-211 or melanosomes may increase IGF2 levels, promoting its binding to IGF1R, and thus leading to hyperactivation of this pathway and increased proliferation.</body> </html> </notes> <label text="IGF2R"/> <bbox w="80.0" h="50.0" x="2172.5" y="322.5"/> <glyph class="unit of information" id="_47f9061b-afdf-4891-b13a-26f064ef6dce"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2190.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4508_gf1_sa53" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:24668028 IGF2 expressed by CAFs promotes tumor growth PMID:11237532 In breast cancers, both IGF-I and IGF-II are expressed in the stromal ???broblasts and expression of IGF-II in particular correlates with tumor progression</body> </html> </notes> <label text="IGF2"/> <bbox w="80.0" h="40.0" x="1922.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4564_gf1_sa55" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IRS1 HUGO:IRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:8621421 Grb2- and Shc-SH2 domain binding to phosphopeptides from rat IRS-1 PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IRS*"/> <bbox w="80.0" h="40.0" x="1952.5" y="757.5"/> <glyph class="state variable" id="_d9a192ac-b880-42a8-8b7d-165bcab98c1c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1945.0" y="772.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4563_gf1_sa56" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IRS1 HUGO:IRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:8621421 Grb2- and Shc-SH2 domain binding to phosphopeptides from rat IRS-1 PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IRS*"/> <bbox w="80.0" h="40.0" x="1952.5" y="657.5"/> <glyph class="state variable" id="_3232804e-00af-4cfa-9661-9507592ad641"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1947.5" y="672.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4565_gf1_sa57" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IGF1R"/> <bbox w="80.0" h="50.0" x="1852.5" y="522.5"/> <glyph class="state variable" id="_c60490bb-1655-4f3f-9486-6e7c2924c8c2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1845.0" y="542.5"/> </glyph> <glyph class="unit of information" id="_46b1502a-4b09-41a4-ba87-b23b663576ed"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1870.0" y="517.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4515_gf1_sa58" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IGF1R"/> <bbox w="80.0" h="50.0" x="1852.5" y="322.5"/> <glyph class="state variable" id="_4138c239-7657-4c3c-93cd-418946c4e78b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1847.5" y="342.5"/> </glyph> <glyph class="unit of information" id="_8e962ec9-9569-4527-af01-6c617157efd7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1870.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4519_gf1_sa59" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 20388853 Upon binding by either IGF-1 or IGF-2, the IGF-1R undergoes receptor cross-linking and autophosphorylation, leading to the creation of multiple docking sites for the adaptor proteins IRS-1, IRS-2, and Shc.</body> </html> </notes> <label text="IGF1"/> <bbox w="80.0" h="40.0" x="2072.5" y="127.5"/> </glyph> <glyph class="source and sink" id="gf1_s4597_gf1_sa63" compartmentRef="gf1_c1_gf1_ca1"> <label text="csa102_degraded"/> <bbox w="30.0" h="30.0" x="2247.5" y="662.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4529_gf1_sa65" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MET MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121; PMID:20303741 Upon HGF binding, Met autophosphorylation occurs on tyrosine residues Y1234 and Y1235 (numbered according to GenBank J02958) within the activation loop of the TK domain, inducing kinase activity, while phosphorylation on Y1349 and Y1356 near the carboxyl terminus forms a docking site for intracellular adapters that transmit signals downstream.6, 8 An intact docking site is required for transformation and metastasis.8 Critical signalling mediators in this pathway include Grb2, Gab1, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma (PLC??), Shc, Src, Shp2, Ship1 and STAT3.6, 8</body> </html> </notes> <label text="MET"/> <bbox w="80.0" h="50.0" x="2372.5" y="322.5"/> <glyph class="state variable" id="_227dae45-6856-4b81-8d39-67a0069a88f5"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2367.5" y="342.5"/> </glyph> <glyph class="unit of information" id="_d0961bd5-23c9-4c2b-9481-d78c3a272695"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2390.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4468_gf1_sa66" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:HGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121 Hepatocyte growth factor (HGF) induces cancer cell migration and invasion.</body> </html> </notes> <label text="HGF"/> <bbox w="80.0" h="40.0" x="2462.5" y="127.5"/> </glyph> <glyph class="complex" id="gf1_s417_gf1_csa8" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>PMID:7682895; PMID:17397400 PDGF -receptor directly binds and activates PLC-gamma 1, RasGAP, P13K, and a 64 kd protein. PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts downstream of PDGF signaling</body> </html> </notes> <label text="gf1_s417"/> <bbox w="100.0" h="130.0" x="212.5" y="492.5"/> <glyph class="macromolecule" id="gf1_s413_gf1_sa106"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PGDFRA HUGO:PGDFRB MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR alpha and beta, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGFRA binds to all PDGF isoforms except PDGF-DD, while PDGFRB is activated by PDGF-BB and -DD. PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells . The large protein complex recruited by phosphorylated PDGF receptors is seen as a dynamic signalosome that controls cell fate.</body> </html> </notes> <label text="PDGFR*"/> <bbox w="80.0" h="50.0" x="222.5" y="552.5"/> <glyph class="unit of information" id="_c4144bc4-a27b-4307-8729-50e48cab343e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="240.0" y="547.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s424_gf1_sa107"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PDGFA HUGO:PDGFB HUGO:PDGFC HUGO:PDGFD MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23123598 PDGF stimulation of CAFs induces production of the prototypical pro-angiogenic inducer fibroblast growth factor (FGF)-2 in both cervical carcinomas and melanoma [11] and [85]. Interestingly, CAFs activated by PDGF-CC in melanomas also secrete the extracellular matrix protein osteopontin, the action of which is known to synergistically stimulate angiogenesis together with FGF-2 and promote autocrine VEGF-A signaling in endothelial cells PMID:15207817; PMID:19118022 PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Tumor fibroblasts a recruted by PDGF PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR?? and ??, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells</body> </html> </notes> <label text="PDGF*"/> <bbox w="80.0" h="40.0" x="222.5" y="507.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s419_gf1_csa10" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s419"/> <bbox w="100.0" h="142.5" x="1172.5" y="506.25"/> <glyph class="macromolecule" id="gf1_s421_gf1_sa110"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:EGFR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40). PMID:28513565 Epidermal growth factor receptor (EGFR) signaling pathways leading to G1/S cell cycle progression activated by EGF activation. Depicted are the RAS-RAF-MEK-ERK MAPK and PI3K-AKT-mTOR pathways. Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)", ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="EGFR"/> <bbox w="80.0" h="50.0" x="1182.5" y="523.75"/> <glyph class="unit of information" id="_13486e9e-383c-46e4-90bc-348f391b34f6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1200.0" y="518.75"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s422_gf1_sa111"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:ERBB2 HUGO:ERBB3 HUGO:ERBB4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40).</body> </html> </notes> <label text="ERBB*"/> <bbox w="80.0" h="50.0" x="1182.5" y="573.75"/> <glyph class="unit of information" id="_6db49f90-8343-4e05-b0b5-bf1ecf474d7f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1200.0" y="568.75"/> </glyph> </glyph> </glyph> <glyph class="complex" id="gf1_s4594_gf1_csa13" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s4594"/> <bbox w="100.0" h="120.0" x="2102.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s4807_gf1_sa116"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2R MODULE:GROWTH_FACTORS_SIGNALING_PATHWAYS PMID:27548915 One function of IGF2R is to bind to the ligand IGF2, leading to IGF2 degradation and consequently an inhibition of the growth stimulation that results from the interaction between IGF2 and IGF1R48, 49. IGF2 is upregulated in CAFs50, suggesting that IGF2R is inhibited. Therefore, reduction in IGF2R following treatment with miR-211 or melanosomes may increase IGF2 levels, promoting its binding to IGF1R, and thus leading to hyperactivation of this pathway and increased proliferation.</body> </html> </notes> <label text="IGF2R"/> <bbox w="80.0" h="50.0" x="2112.5" y="572.5"/> <glyph class="unit of information" id="_0570584b-b192-4067-8e1a-c08dddd12cc1"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2130.0" y="567.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4596_gf1_sa117"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:24668028 IGF2 expressed by CAFs promotes tumor growth PMID:11237532 In breast cancers, both IGF-I and IGF-II are expressed in the stromal ???broblasts and expression of IGF-II in particular correlates with tumor progression</body> </html> </notes> <label text="IGF2"/> <bbox w="80.0" h="40.0" x="2112.5" y="527.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s4530_gf1_csa15" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s4530"/> <bbox w="100.0" h="120.0" x="2452.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s4825_gf1_sa120"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:HGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121 Hepatocyte growth factor (HGF) induces cancer cell migration and invasion.</body> </html> </notes> <label text="HGF"/> <bbox w="80.0" h="40.0" x="2462.5" y="527.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4826_gf1_sa121"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MET MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121; PMID:20303741 Upon HGF binding, Met autophosphorylation occurs on tyrosine residues Y1234 and Y1235 (numbered according to GenBank J02958) within the activation loop of the TK domain, inducing kinase activity, while phosphorylation on Y1349 and Y1356 near the carboxyl terminus forms a docking site for intracellular adapters that transmit signals downstream.6, 8 An intact docking site is required for transformation and metastasis.8 Critical signalling mediators in this pathway include Grb2, Gab1, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma (PLC??), Shc, Src, Shp2, Ship1 and STAT3.6, 8</body> </html> </notes> <label text="MET"/> <bbox w="80.0" h="50.0" x="2462.5" y="572.5"/> <glyph class="state variable" id="_3021eab2-66b1-438d-9ea7-91b15b2d2dd2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2455.0" y="592.5"/> </glyph> <glyph class="unit of information" id="_555cd1e1-402e-4b39-8601-4ccbf260dcca"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2480.0" y="567.5"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s1_gf1_sa130" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:TGFA MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="TGFA"/> <bbox w="80.0" h="40.0" x="1102.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s2_gf1_sa131" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:NRG1 HUGO:NRG2 HUGO:NRG3 HUGO:NRG4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="NRG*"/> <bbox w="80.0" h="40.0" x="1282.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s3_gf1_sa132" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:BTC MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="BTC"/> <bbox w="80.0" h="40.0" x="1002.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4_gf1_sa133" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:EREG MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="EREG"/> <bbox w="80.0" h="40.0" x="1612.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s5_gf1_sa134" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:HBEGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="HBEGF"/> <bbox w="80.0" h="40.0" x="902.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s6_gf1_sa135" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:EPGN MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="EPGN"/> <bbox w="80.0" h="40.0" x="1382.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s5191_gf1_sa136" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3262.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s3913_gf1_sa138" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS HUGO:FLT1 PMID: 28560064 Expression of Flt1 promotes glioblastoma cells migration, invasion</body> </html> </notes> <label text="FLT1"/> <bbox w="80.0" h="50.0" x="3602.5" y="322.5"/> <glyph class="unit of information" id="_a0875011-b423-430c-8a85-56bc26a7f962"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3620.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s7_gf1_sa143" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FLT4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16530705 The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells</body> </html> </notes> <label text="FLT4"/> <bbox w="80.0" h="50.0" x="2982.5" y="322.5"/> <glyph class="unit of information" id="_d63a3aa2-2849-4bef-8759-d815fed4e5b8"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3000.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s8_gf1_sa144" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:MST1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. Identifiers_begin: macrophage stimulating 1 (hepatocyte growth factor-like) D3F15S2 DNF15S2 HGFL HUGO:MST1 HGNC:7380 ENTREZ:4485 UNIPROT:P26927 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="MST1"/> <bbox w="80.0" h="40.0" x="2672.5" y="127.5"/> <glyph class="state variable" id="_4f7dfb7d-f969-4df8-976f-b27c05239a03"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2667.5" y="142.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s9_gf1_sa145" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MST1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. RON activation results in the autophosphorylation of Tyr1238 and Tyr1239 at the A-loop (Phe1227???Pro1250) in the kinase domain93,95,98. Phosphorylation of these regulatory residues then activates the kinase activity, leading to further phosphorylation of Tyr1353 and Tyr1360 in the C-terminal docking site. The docking site interacts with downstream signalling proteins, triggering multiple intracellular pathways MSP???RON signalling activates two classical signalling pathways, RAS???ERK and PI3K???AKT, both of which interact with various other pathways to create a complex signalling network.</body> </html> </notes> <label text="MST1R"/> <bbox w="80.0" h="50.0" x="2802.5" y="322.5"/> <glyph class="state variable" id="_8d5a1203-c48d-45f6-98eb-d1abbd577a22"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2797.5" y="342.5"/> </glyph> <glyph class="unit of information" id="_ef52596d-d6bf-48f0-9f8c-b3f37d3e2a4e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2820.0" y="317.5"/> </glyph> </glyph> <glyph class="phenotype" id="gf1_s5192_gf1_sa146" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:28513565 EGFR pathways PMID:20388853 IGFR1 pathways PMID:23792360 MST1 pathways PMID:20303741 HGF</body> </html> </notes> <label text="MAPK_PATHWAYS"/> <bbox w="432.5" h="43.75" x="2506.25" y="1085.625"/> </glyph> <glyph class="phenotype" id="gf1_s5193_gf1_sa147" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:28513565 EGFR pathways PMID:28475121 HGF/MET PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="PLCG_PATHWAYS"/> <bbox w="435.0" h="47.5" x="1195.0" y="1053.75"/> </glyph> <glyph class="phenotype" id="gf1_s5194_gf1_sa148" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:28513565 EGFR pathways PMID: 20388853 IGF1R PMID:23792360 MST1 pathways PMID:28475121 HGF/MET PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="PI3K_PATHWAY"/> <bbox w="415.0" h="42.5" x="1815.0" y="1146.25"/> </glyph> <glyph class="phenotype" id="gf1_s5196_gf1_sa150" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:24675568 EGFR/JAK/STAT STAT3 is a critical mediator of the oncogenic effects of EGFR mutations PMID:20303741 HGF</body> </html> </notes> <label text="JAK/STAT_PATHWAY"/> <bbox w="345.0" h="42.5" x="710.0" y="1146.25"/> </glyph> <glyph class="macromolecule" id="gf1_s5197_gf1_sa151" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KL MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 The Fgf15/19 subfamily members encode endocrine FGFs, which bind to and activate FGFRs with the Klotho family protein as a cofactor.</body> </html> </notes> <label text="KL"/> <bbox w="80.0" h="40.0" x="902.5" y="547.5"/> </glyph> <glyph class="macromolecule" id="gf1_s5198_gf1_sa152" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KLB MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 The Fgf15/19 subfamily members encode endocrine FGFs, which bind to and activate FGFRs with the Klotho family protein as a cofactor.</body> </html> </notes> <label text="KLB"/> <bbox w="80.0" h="40.0" x="902.5" y="467.5"/> </glyph> <glyph class="simple chemical" id="gf1_s5199_gf1_sa153" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Canonical FGFs are tightly bound to heparin/heparan sulfate (HS) proteoglycans (HSPGs), which function to limit diffusion through the extracellular matrix (ECM) and serve as cofactors that regulate specificity and affinity for signaling FGFRs.</body> </html> </notes> <label text="HSPGs*"/> <bbox w="70.0" h="25.0" x="907.5" y="395.0"/> </glyph> <glyph class="complex" id="gf1_s5200_gf1_csa22" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s5200"/> <bbox w="100.0" h="120.0" x="622.5" y="507.5"/> <glyph class="macromolecule" id="gf1_s5201_gf1_sa41"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGFR1 HUGO:FGFR2 HUGO:FGFR3 HUGO:FGFR4 HUGO:FGFRL1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25467007 FGFRs _rew PMID:25772309 Binding of canonical FGFs to FGFR with HS (or HSPG) as a cofactor induces the formation of ternary FGF???FGFR???HS complex, which activates the FGFR intracellular tyrosine kinase domain by phosphorylation of specific tyrosine residues. The activated receptor is coupled to intracellular signaling pathways including the RAS???MAPK, PI3K???AKT, PLC??, and STAT pathways.</body> </html> </notes> <label text="FGFR*"/> <bbox w="80.0" h="50.0" x="632.5" y="562.5"/> <glyph class="unit of information" id="_7d803cf0-0f78-4048-b5bf-920c3cd3713c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="650.0" y="557.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s5202_gf1_sa154"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGF1 HUGO:FGF2 HUGO:FGF3 HUGO:FGF4 HUGO:FGF5 HUGO:FGF6 HUGO:FGF7 HUGO:FGF8 HUGO:FGF9 HUGO:FGF10 HUGO:FGF11 HUGO:FGF12 HUGO:FGF13 HUGO:FGF14 HUGO:FGF16 HUGO:FGF17 HUGO:FGF18 HUGO:FGF19 HUGO:FGF20 HUGO:FGF21 HUGO:FGF22 HUGO:FGF23 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Deregulation of FGF signaling pathways have been implicated in many types of human and animal cancers.</body> </html> </notes> <label text="FGF*"/> <bbox w="80.0" h="40.0" x="632.5" y="517.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s5203_gf1_csa23" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s5203"/> <bbox w="100.0" h="120.0" x="2662.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s5204_gf1_sa156"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:MST1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. Identifiers_begin: macrophage stimulating 1 (hepatocyte growth factor-like) D3F15S2 DNF15S2 HGFL HUGO:MST1 HGNC:7380 ENTREZ:4485 UNIPROT:P26927 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="MST1"/> <bbox w="80.0" h="40.0" x="2672.5" y="527.5"/> <glyph class="state variable" id="_d931b33d-72e8-42dd-a4dd-4130e2586bf9"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2667.5" y="542.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s5205_gf1_sa157"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MST1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. RON activation results in the autophosphorylation of Tyr1238 and Tyr1239 at the A-loop (Phe1227???Pro1250) in the kinase domain93,95,98. Phosphorylation of these regulatory residues then activates the kinase activity, leading to further phosphorylation of Tyr1353 and Tyr1360 in the C-terminal docking site. 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xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FLT4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16530705 The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells</body> </html> </notes> <label text="FLT4"/> <bbox w="80.0" h="50.0" x="3042.5" y="562.5"/> <glyph class="unit of information" id="_08655090-509c-4c49-a4f1-a36a8c17c0d6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3060.0" y="557.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s5208_gf1_sa159"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3042.5" y="527.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s3866_gf1_sa137" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KDR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:17883421 Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer</body> </html> </notes> <label text="KDR"/> <bbox w="80.0" h="50.0" x="3252.5" y="322.5"/> <glyph class="unit of information" id="_02ed7b2e-e650-4793-b8a1-641d5b292e86"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3270.0" y="317.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s5209_gf1_csa20" compartmentRef="gf1_c1_gf1_ca1"> <label text="KDR:VEGF*"/> <bbox w="100.0" h="120.0" x="3292.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s3910_gf1_sa139"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KDR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:17883421 Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer</body> </html> </notes> <label text="KDR"/> <bbox w="80.0" h="50.0" x="3302.5" y="572.5"/> <glyph class="unit of information" id="_9dafa460-33d8-45cf-b0af-045bd3c89b6e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3320.0" y="567.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s3911_gf1_sa140"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3302.5" y="527.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s5210_gf1_csa21" compartmentRef="gf1_c1_gf1_ca1"> <label text="FLT1:VEGF*"/> <bbox w="100.0" h="130.0" x="3542.5" y="512.5"/> <glyph class="macromolecule" id="gf1_s4495_gf1_sa142"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3552.5" y="517.5"/> </glyph> <glyph class="macromolecule" id="gf1_s3915_gf1_sa141"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS HUGO:FLT1 PMID: 28560064 Expression of Flt1 promotes glioblastoma cells migration, invasion</body> </html> </notes> <label text="FLT1"/> <bbox w="80.0" h="50.0" x="3552.5" y="572.5"/> <glyph class="unit of information" id="_7f54f128-764c-40c3-b64a-d49391973b84"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3570.0" y="567.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s23_mpk1_mpk1_csa75" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TNFRSF1B:TRAF2 Identifiers_end</body> </html> </notes> <label text="TNFRSF1B:TRAF2"/> <bbox w="132.0" h="80.0" x="2725.9963" y="1509.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s727_mpk1_mpk1_sa439"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2765.4963" y="1540.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s24_mpk1_mpk1_sa440"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1B TNFR2 HUGO:TNFRSF1B HGNC:11917 ENTREZ:7133 UNIPROT:P20333 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins (TRAF2). PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1B"/> <bbox w="70.0" h="25.0" x="2757.4963" y="1516.0"/> <glyph class="unit of information" id="_0022ef53-ef9f-4182-8d9e-bbb6c705158a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2769.9963" y="1511.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s14_mpk1_mpk1_csa74" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:RIPK1:TNFRSF1A:TRADD:TRAF2 Identifiers_end</body> </html> </notes> <label text="RIPK1:TNFRSF1A:TRADD:TRAF2"/> <bbox w="216.0" h="85.0" x="2445.9963" y="1647.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s18_mpk1_mpk1_sa436"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNFRSF1A-associated via death domain HUGO:TRADD HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TRADD"/> <bbox w="50.0" h="25.0" x="2567.4963" y="1655.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s19_mpk1_mpk1_sa437"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2504.4963" y="1680.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s20_mpk1_mpk1_sa438"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: receptor (TNFRSF)-interacting serine-threonine kinase 1 HUGO:RIPK1 HGNC:10019 ENTREZ:8737 UNIPROT:Q13546 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TNF treatment is thought to result in the formation of a TRADD-RIP-TRAF2 complex at the membrane. PMID:11274345 References_end</body> </html> </notes> <label text="RIPK1"/> <bbox w="50.0" h="25.0" x="2554.4963" y="1680.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s831_mpk1_mpk1_sa593"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1A TNFR1 HUGO:TNFRSF1A HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1A"/> <bbox w="70.0" h="25.0" x="2496.4546" y="1656.0"/> <glyph class="unit of information" id="_db03f7ae-22e3-47b2-86d5-d363581a63a0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2508.9546" y="1651.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s15_mpk1_mpk1_csa72" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TNFRSF1A:TRADD:TRAF2 Identifiers_end</body> </html> </notes> <label text="TNFRSF1A:TRADD:TRAF2"/> <bbox w="180.0" h="113.0" x="2451.9963" y="1501.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s1_mpk1_mpk1_sa430"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNFRSF1A-associated via death domain HUGO:TRADD HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TRADD"/> <bbox w="55.0" h="25.0" x="2512.9963" y="1535.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s2_mpk1_mpk1_sa431"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1A TNFR1 HUGO:TNFRSF1A HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1A"/> <bbox w="70.0" h="25.0" x="2507.9963" y="1511.0"/> <glyph class="unit of information" id="_9abb73ee-fb8b-4721-82ae-b26d697f571e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2520.4963" y="1506.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s3_mpk1_mpk1_sa432"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2514.9963" y="1561.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s16_mpk1_mpk1_csa73" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TNFRSF1A:TRADD Identifiers_end</body> </html> </notes> <label text="TNFRSF1A:TRADD"/> <bbox w="126.0" h="83.0" x="2421.9963" y="1392.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s7_mpk1_mpk1_sa434"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNFRSF1A-associated via death domain HUGO:TRADD HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TRADD"/> <bbox w="50.0" h="25.0" x="2459.4963" y="1424.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s830_mpk1_mpk1_sa592"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1A TNFR1 HUGO:TNFRSF1A HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1A"/> <bbox w="70.0" h="25.0" x="2450.0" y="1401.0"/> <glyph class="unit of information" id="_5997f1e3-b729-494f-aabd-4804947302e7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2462.5" y="1396.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s49_mpk1_mpk1_csa80" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TGFBR1:TGFBR2 Identifiers_end</body> </html> </notes> <label text="TGFBR1:TGFBR2"/> <bbox w="130.0" h="64.0" x="3419.9963" y="1314.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s46_mpk1_mpk1_sa453"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor 1 "transforming growth factor beta receptor I (activin A receptor type II-like kinase 53kD)" HUGO:TGFBR1 HGNC:11772 ENTREZ:7046 UNIPROT:P36897 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR1"/> <bbox w="55.0" h="25.0" x="3430.9963" y="1325.0"/> <glyph class="unit of information" id="_4ea1af92-9f2a-40d7-9123-21f4c106d0de"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3435.9963" y="1320.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s47_mpk1_mpk1_sa454"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor II (70/80kDa) MFS2 "transforming growth factor beta receptor II (70-80kD)" HUGO:TGFBR2 HGNC:11773 ENTREZ:7048 UNIPROT:P37173 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR2"/> <bbox w="55.0" h="25.0" x="3485.9963" y="1326.0"/> <glyph class="unit of information" id="_ab15a528-3969-486a-98ab-a3980c795b93"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3490.9963" y="1321.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1000_mpk1_mpk1_csa76" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TAB*:TGFBR1:TGFBR2 Identifiers_end</body> </html> </notes> <label text="TAB*:TGFBR1:TGFBR2"/> <bbox w="143.0" h="81.0" x="3285.9963" y="1619.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s728_mpk1_mpk1_sa443"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TGF-beta activated kinase 1/MAP3K7 binding protein 1 MAP3K7IP1 "mitogen-activated protein kinase kinase kinase 7 interacting protein 1" HUGO:TAB1 HGNC:18157 ENTREZ:10454 UNIPROT:Q15750 TGF-beta activated kinase 1/MAP3K7 binding protein 2 MAP3K7IP2 "mitogen-activated protein kinase kinase kinase 7 interacting protein 2" HUGO:TAB2 HGNC:17075 ENTREZ:23118 UNIPROT:Q9NYJ8 TGF-beta activated kinase 1/MAP3K7 binding protein 3 MAP3K7IP3 "mitogen-activated protein kinase kinase kinase 7 interacting protein 3" HUGO:TAB3 HGNC:30681 ENTREZ:257397 UNIPROT:Q8N5C8 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TAK1 is the only MAP3K that requires the adapter proteins TAB123 for its activation. PMID:20060931 References_end</body> </html> </notes> <label text="TAB*"/> <bbox w="50.0" h="25.0" x="3301.163" y="1650.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s835_mpk1_mpk1_sa597"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor 1 "transforming growth factor beta receptor I (activin A receptor type II-like kinase 53kD)" HUGO:TGFBR1 HGNC:11772 ENTREZ:7046 UNIPROT:P36897 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR1"/> <bbox w="55.0" h="25.0" x="3301.2727" y="1629.0"/> <glyph class="unit of information" id="_62ea3e7e-dca8-4ab8-983f-a00ce0d3f00b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3306.2727" y="1624.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s55_mpk1_mpk1_sa598"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor II (70/80kDa) MFS2 "transforming growth factor beta receptor II (70-80kD)" HUGO:TGFBR2 HGNC:11773 ENTREZ:7048 UNIPROT:P37173 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR2"/> <bbox w="55.0" h="25.0" x="3357.2727" y="1630.0"/> <glyph class="unit of information" id="_e823a417-2438-4391-812c-17ec77473be3"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3362.2727" y="1625.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s981_mpk1_mpk1_csa31" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:RTK*:SRC Identifiers_end</body> </html> </notes> <label text="RTK*:SRC"/> <bbox w="72.0" h="88.0" x="198.0" y="1403.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s273_mpk1_mpk1_sa164"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 GENECARDS:SRC REACTOME:402877 KEGG:6714 ATLASONC:SRCID448ch20q11 WIKI:SRC Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end</body> </html> </notes> <label text="SRC"/> <bbox w="50.0" h="25.0" x="207.0" y="1438.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s820_mpk1_mpk1_sa582"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="208.27272" y="1417.0"/> <glyph class="state variable" id="_f5321eac-0dbb-43ce-96be-c326882f6f21"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="253.27272" y="1429.6776"/> </glyph> <glyph class="state variable" id="_d5e2973a-53ba-4be1-aca2-453878bfa86c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="253.27272" y="1429.6776"/> </glyph> <glyph class="state variable" id="_9803efb0-8fbd-4569-8afc-a897e5ee6141"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="253.27272" y="1424.5"/> </glyph> <glyph class="unit of information" id="_353967c9-5587-49c8-b8bd-b7ddf09cfb3e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="210.77272" y="1412.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s987_mpk1_mpk1_csa32" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:PLCG1:RTK*:SRC Identifiers_end</body> </html> </notes> <label text="PLCG1:RTK*:SRC"/> <bbox w="113.0" h="115.0" x="215.0" y="1521.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s284_mpk1_mpk1_sa173"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 GENECARDS:SRC REACTOME:402877 KEGG:6714 ATLASONC:SRCID448ch20q11 WIKI:SRC Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end</body> </html> </notes> <label text="SRC"/> <bbox w="50.0" h="25.0" x="245.0" y="1557.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s285_mpk1_mpk1_sa174"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: phospholipase C gamma 1 "phospholipase C gamma 1 (formerly subtype 148)" PLC1 HUGO:PLCG1 HGNC:9065 ENTREZ:5335 UNIPROT:P19174 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In response to Src-dependent activation of PLCG1 RasGRP1 translocated to the Golgi where it activated Ras. PMID:12845332 References_end</body> </html> </notes> <label text="PLCG1"/> <bbox w="50.0" h="25.0" x="245.0" y="1582.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s821_mpk1_mpk1_sa583"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="245.27272" y="1534.0"/> <glyph class="state variable" id="_23401b8b-0535-4420-b5ed-7545fc8f7012"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="290.2727" y="1546.6776"/> </glyph> <glyph class="state variable" id="_0024d82d-b012-469b-9d9c-0ef95b330bb3"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="290.2727" y="1546.6776"/> </glyph> <glyph class="state variable" id="_9fa774c5-c1ee-40d8-937a-69086107bf23"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="290.2727" y="1541.5"/> </glyph> <glyph class="unit of information" id="_7b146f29-e885-4544-acd9-ded81736812c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="247.77272" y="1529.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s32_mpk1_mpk1_csa77" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL1R1:MYD88 Identifiers_end</body> </html> </notes> <label text="IL1R1:MYD88"/> <bbox w="97.0" h="81.0" x="3071.9963" y="1437.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s33_mpk1_mpk1_sa445"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: myeloid differentiation primary response 88 "myeloid differentiation primary response gene (88)" HUGO:MYD88 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: The IL-1R/IL-1RAcP heterodimer recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="MYD88"/> <bbox w="59.0" h="24.0" x="3090.4963" y="1468.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s833_mpk1_mpk1_sa596"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 1 receptor type I IL1R IL1RA HUGO:IL1R1 HGNC:5993 ENTREZ:3554 UNIPROT:P14778 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IL-1 likely requires TRAF6 to signal to the SAPKs. IL-1 binding to its receptor (IL-1R) triggers heterodimerisation of IL-1R with IL-1RAcP (not modelled) a transmembrane protein necessary for IL-1 signal transduction. The IL-1R/IL-1RAcP heterodimer then recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="IL1R1"/> <bbox w="50.0" h="25.0" x="3095.4546" y="1446.0"/> <glyph class="unit of information" id="_e1c9e259-6b8c-4aa2-9ea1-1cc160d1727a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3097.9546" y="1441.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s705_mpk1_mpk1_csa78" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL1R1:IRAK1:MYD88:TRAF6 Identifiers_end</body> </html> </notes> <label text="IL1R1:IRAK1:MYD88:TRAF6"/> <bbox w="190.0" h="85.0" x="3035.9963" y="1658.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s42_mpk1_mpk1_sa447"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: myeloid differentiation primary response 88 "myeloid differentiation primary response gene (88)" HUGO:MYD88 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: The IL-1R/IL-1RAcP heterodimer recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="MYD88"/> <bbox w="56.0" h="25.0" x="3076.4963" y="1692.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s40_mpk1_mpk1_sa448"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin-1 receptor-associated kinase 1 HUGO:IRAK1 HGNC:6112 ENTREZ:3654 UNIPROT:P51617 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Similar to RIP recruitment by TRADD the death domain of receptor-bound MyD88 binds IRAK1. PMID:11274345 References_end</body> </html> </notes> <label text="IRAK1"/> <bbox w="50.0" h="25.0" x="3132.4963" y="1692.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s41_mpk1_mpk1_sa449"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 6 E3 ubiquitin protein ligase "TNF receptor-associated factor 6" HUGO:TRAF6 HGNC:12036 ENTREZ:7189 UNIPROT:Q9Y4K3 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon recruitment to the IL-1R complex IRAK1 binds TRAF6 forming a MyD88-IRAK1-TRAF6 complex analogous to the TNFR-associated complex of TRADD RIP and TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF6"/> <bbox w="50.0" h="25.0" x="3128.4963" y="1666.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s832_mpk1_mpk1_sa594"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 1 receptor type I IL1R IL1RA HUGO:IL1R1 HGNC:5993 ENTREZ:3554 UNIPROT:P14778 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IL-1 likely requires TRAF6 to signal to the SAPKs. IL-1 binding to its receptor (IL-1R) triggers heterodimerisation of IL-1R with IL-1RAcP (not modelled) a transmembrane protein necessary for IL-1 signal transduction. The IL-1R/IL-1RAcP heterodimer then recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="IL1R1"/> <bbox w="50.0" h="25.0" x="3078.4546" y="1668.0"/> <glyph class="unit of information" id="_3f6afa60-2bb0-4e7b-9490-37c76f9a2425"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3080.9546" y="1663.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s999_mpk1_mpk1_csa79" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL1R1:IRAK1:MYD88 Identifiers_end</body> </html> </notes> <label text="IL1R1:IRAK1:MYD88"/> <bbox w="145.0" h="84.0" x="3068.9963" y="1552.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s36_mpk1_mpk1_sa451"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: myeloid differentiation primary response 88 "myeloid differentiation primary response gene (88)" HUGO:MYD88 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: The IL-1R/IL-1RAcP heterodimer recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="MYD88"/> <bbox w="59.0" h="25.0" x="3086.4963" y="1583.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s37_mpk1_mpk1_sa452"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin-1 receptor-associated kinase 1 HUGO:IRAK1 HGNC:6112 ENTREZ:3654 UNIPROT:P51617 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Similar to RIP recruitment by TRADD the death domain of receptor-bound MyD88 binds IRAK1. PMID:11274345 References_end</body> </html> </notes> <label text="IRAK1"/> <bbox w="50.0" h="25.0" x="3145.4963" y="1583.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s834_mpk1_mpk1_sa595"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 1 receptor type I IL1R IL1RA HUGO:IL1R1 HGNC:5993 ENTREZ:3554 UNIPROT:P14778 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IL-1 likely requires TRAF6 to signal to the SAPKs. IL-1 binding to its receptor (IL-1R) triggers heterodimerisation of IL-1R with IL-1RAcP (not modelled) a transmembrane protein necessary for IL-1 signal transduction. The IL-1R/IL-1RAcP heterodimer then recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="IL1R1"/> <bbox w="50.0" h="25.0" x="3090.4546" y="1561.0"/> <glyph class="unit of information" id="_a33d6764-662f-4785-b24d-12ca6771fb4f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3092.9546" y="1556.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s989_mpk1_mpk1_csa6" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RTK*:SOS*"/> <bbox w="109.0" h="104.0" x="791.0" y="1387.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s764_mpk1_mpk1_sa26"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="819.5" y="1440.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s887_mpk1_mpk1_sa27"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="820.5" y="1415.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s888_mpk1_mpk1_sa32"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="821.5" y="1392.5"/> <glyph class="state variable" id="_e60cbcec-0054-4bf0-8c06-8eedd8548ee8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="866.5" y="1405.1776"/> </glyph> <glyph class="state variable" id="_23ce26b9-1088-4a58-ba3d-32471a8d3cd1"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="866.5" y="1405.1776"/> </glyph> <glyph class="state variable" id="_50caaf78-b699-4073-8a50-08a1513e8802"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="866.5" y="1400.0"/> </glyph> <glyph class="unit of information" id="_2ec9604d-cdc1-462d-b384-e101fa03d87c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="824.0" y="1387.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s991_mpk1_mpk1_csa3" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RAS*:RTK*:SOS*"/> <bbox w="143.0" h="103.0" x="876.0" y="1657.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s758_mpk1_mpk1_sa11"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="901.0" y="1713.0"/> <glyph class="state variable" id="_03a32025-6e7e-4b83-82c6-246395c79c74"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="893.5" y="1720.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s759_mpk1_mpk1_sa15"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="949.5" y="1715.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s760_mpk1_mpk1_sa30"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="950.5" y="1688.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s761_mpk1_mpk1_sa34"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="950.5" y="1665.5"/> <glyph class="state variable" id="_823cc8ac-9f45-436a-86f6-e1d0ab751574"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="995.5" y="1678.1776"/> </glyph> <glyph class="state variable" id="_26dfca1c-d21a-4832-a857-7687d486c2f6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="995.5" y="1678.1776"/> </glyph> <glyph class="state variable" id="_1f0ff98d-0c84-44e5-90ea-cb0ad634b239"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="995.5" y="1673.0"/> </glyph> <glyph class="unit of information" id="_82d1cceb-4290-47e5-869a-be3cc760b09b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="953.0" y="1660.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s992_mpk1_mpk1_csa68" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RAF1:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RAF1:RAS*:RTK*:SOS*"/> <bbox w="185.0" h="106.0" x="1150.0" y="1641.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s752_mpk1_mpk1_sa333"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1271.0" y="1674.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s753_mpk1_mpk1_sa334"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1270.0" y="1699.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s572_mpk1_mpk1_sa337"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="1166.0" y="1699.0"/> <glyph class="state variable" id="_a8cc4159-df92-443d-8152-f2b6a34326f9"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1158.5" y="1707.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s824_mpk1_mpk1_sa585"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1271.0" y="1651.0"/> <glyph class="state variable" id="_742a9d15-fd7e-4df3-a356-ad5c7f6a2e7a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1316.0" y="1663.6776"/> </glyph> <glyph class="state variable" id="_0eb6014a-bc72-4a54-a570-0f600a8047be"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1316.0" y="1663.6776"/> </glyph> <glyph class="state variable" id="_c84b5a3d-ee91-4d8a-ac5c-5a068f1a80e7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1316.0" y="1658.5"/> </glyph> <glyph class="unit of information" id="_6a7045dc-fccf-4920-9639-a66d6ef8010a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1273.5" y="1646.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s858_mpk1_mpk1_sa619"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1227.375" y="1698.5"/> <glyph class="state variable" id="_393a9e32-5d8c-4b46-8579-58fef0a14eff"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1219.875" y="1706.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s990_mpk1_mpk1_csa99" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RAC1:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RAC1:RTK*:SOS*"/> <bbox w="152.0" h="103.0" x="1168.9965" y="1393.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s621_mpk1_mpk1_sa522"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1248.4965" y="1421.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s622_mpk1_mpk1_sa523"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1248.4965" y="1445.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s624_mpk1_mpk1_sa524"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end Identifiers_begin: Ras-related C3 botulin toxin substrate 1 (rho family, small GTP binding protein Rac1 HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 GENECARDS:RAC1 REACTOME:404635 KEGG:5879 ATLASONC:GC_RAC1 WIKI:RAC1 ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:18000759 PMID:19151919 Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end</body> </html> Identifiers_begin: Ras-related C3 botulin toxin substrate 1 (rho family, small GTP binding protein Rac1 HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 GENECARDS:RAC1 REACTOME:404635 KEGG:5879 ATLASONC:GC_RAC1 WIKI:RAC1 ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:18000759 PMID:19151919 Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end</body> </html> Identifiers_begin: Ras-related C3 botulin toxin substrate 1 (rho family, small GTP binding protein Rac1 HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 GENECARDS:RAC1 REACTOME:404635 KEGG:5879 ATLASONC:GC_RAC1 WIKI:RAC1 ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:18000759 PMID:19151919 Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end</body> </html> </notes> <label text="RAC1"/> <bbox w="60.0" h="25.0" x="1194.4965" y="1445.0"/> <glyph class="state variable" id="_6a9a87e5-92ba-4ee1-86d8-7d08d59982b3"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1186.9965" y="1452.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s822_mpk1_mpk1_sa587"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1249.0" y="1401.0"/> <glyph class="state variable" id="_dba5ccf0-7364-4409-bc32-0dee5597ea9b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1294.0" y="1413.6776"/> </glyph> <glyph class="state variable" id="_e0dc7f31-61aa-44a0-8b9e-6ec331f14397"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1294.0" y="1413.6776"/> </glyph> <glyph class="state variable" id="_5993c183-2121-4e9f-a911-05fef9fb9533"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1294.0" y="1408.5"/> </glyph> <glyph class="unit of information" id="_00adca0a-82a5-4897-8168-dbaa2b3c4ebf"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1251.5" y="1396.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s997_mpk1_mpk1_csa64" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GPCR*:GRK* Identifiers_end</body> </html> </notes> <label text="GPCR*:GRK*"/> <bbox w="81.0" h="81.0" x="2197.0" y="1414.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s543_mpk1_mpk1_sa316"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2215.0" y="1447.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s871_mpk1_mpk1_sa590"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="66.0" h="26.0" x="2207.0" y="1426.0"/> <glyph class="state variable" id="_73143b31-e5e4-4f28-89a7-6265ff6307f4"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2199.5" y="1434.0"/> </glyph> <glyph class="unit of information" id="_1f232837-f76b-4f36-bb05-8ef2221f48f2"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2217.5" y="1421.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s26_mpk1_mpk1_csa81" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERN1:TRAF2 Identifiers_end</body> </html> </notes> <label text="ERN1:TRAF2"/> <bbox w="88.0" h="87.0" x="2895.9963" y="1498.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s28_mpk1_mpk1_sa455"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2915.4963" y="1533.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s84_mpk1_mpk1_sa456"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: endoplasmic reticulum to nucleus signaling 1 "ER to nucleus signalling 1" HUGO:ERN1 HGNC:3449 ENTREZ:2081 UNIPROT:O75460 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: ER stress lead to the oligomerisation and activation of mammalian Ire1p (ERN1). ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="ERN1"/> <bbox w="50.0" h="25.0" x="2916.4963" y="1506.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s982_mpk1_mpk1_csa33" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DAG:RASGRP1 Identifiers_end</body> </html> </notes> <label text="DAG:RASGRP1"/> <bbox w="103.0" h="82.0" x="379.0" y="1406.0"/> <glyph class="simple chemical" id="mpk1_mpk1_s293_mpk1_mpk1_sa178"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Diacylglycerol CAS:N/A PUBCHEM:3914 CHEBI:17815 KEGGCOMPOUND:C00165 Identifiers_end Maps_Modules_begin: MODULE:MAPK Maps_Modules_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="394.0" y="1414.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s291_mpk1_mpk1_sa179"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="398.0" y="1439.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s988_mpk1_mpk1_csa34" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RASGRP1"/> <bbox w="141.0" h="85.0" x="449.5" y="1507.5"/> <glyph class="simple chemical" id="mpk1_mpk1_s890_mpk1_mpk1_sa181"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Diacylglycerol CAS:N/A PUBCHEM:3914 CHEBI:17815 KEGGCOMPOUND:C00165 Identifiers_end Maps_Modules_begin: MODULE:MAPK Maps_Modules_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="496.5" y="1517.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s891_mpk1_mpk1_sa182"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="500.5" y="1542.5"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s892_mpk1_mpk1_sa273"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="455.0" y="1526.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1001_mpk1_mpk1_csa35" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RASGRP1"/> <bbox w="144.0" h="84.0" x="394.0" y="2135.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s838_mpk1_mpk1_sa185"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="450.0" y="2168.0"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s839_mpk1_mpk1_sa274"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="402.44446" y="2151.4443"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s837_mpk1_mpk1_sa600"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Generic_begin: DAG Generic_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="446.125" y="2143.75"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s983_mpk1_mpk1_csa110" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:PKC* Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:PKC*"/> <bbox w="117.0" h="91.0" x="560.0" y="1385.0"/> <glyph class="simple chemical" id="mpk1_mpk1_s935_mpk1_mpk1_sa688"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Diacylglycerol CAS:N/A PUBCHEM:3914 CHEBI:17815 KEGGCOMPOUND:C00165 Identifiers_end Maps_Modules_begin: MODULE:MAPK Maps_Modules_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="600.0" y="1392.5"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s934_mpk1_mpk1_sa689"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="564.5" y="1406.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s936_mpk1_mpk1_sa690"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: protein kinase C alpha PKCA HUGO:PRKCA HGNC:9393 ENTREZ:5578 UNIPROT:P17252 protein kinase C beta PKCB PRKCB1 PRKCB2 "protein kinase C beta 1" HUGO:PRKCB HGNC:9395 ENTREZ:5579 UNIPROT:P05771 protein kinase C gamma PKCG SCA14 HUGO:PRKCG HGNC:9402 ENTREZ:5582 UNIPROT:P05129 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity. PMID:15567848 References_end Identifiers_begin: protein kinase C alpha PKCA HUGO:PRKCA HGNC:9393 ENTREZ:5578 UNIPROT:P17252 GENECARDS:PRKCA REACTOME:58197 KEGG:5578 ATLASONC:GC_PRKCA WIKI:PRKCA protein kinase C beta PKCB PRKCB1 PRKCB2 "protein kinase C beta 1" HUGO:PRKCB HGNC:9395 ENTREZ:5579 UNIPROT:P05771 GENECARDS:PRKCB REACTOME:58199 KEGG:5579 ATLASONC:GC_PRKCB WIKI:PRKCB protein kinase C gamma PKCG SCA14 HUGO:PRKCG HGNC:9402 ENTREZ:5582 UNIPROT:P05129 GENECARDS:PRKCG REACTOME:58205 KEGG:5582 ATLASONC:GC_PRKCG WIKI:PRKCG protein kinase C, delta HUGO:PRKCD HGNC:9399 ENTREZ:5580 UNIPROT:Q05655 GENECARDS:PRKCD REACTOME:58201 KEGG:5580 ATLASONC:PRKCDID42901ch3p21 WIKI:PRKCD protein kinase C, epsilon HUGO:PRKCE HGNC:9401 ENTREZ:5581 UNIPROT:Q02156 GENECARDS:PRKCE REACTOME:58203 KEGG:5581 ATLASONC:GC_PRKCE WIKI:PRKCE protein kinase C, eta HUGO:PRKCH HGNC:9403 ENTREZ:5583 UNIPROT:P24723 GENECARDS:PRKCH REACTOME:58209 KEGG:5583 ATLASONC:GC_PRKCH WIKI:PRKCH protein kinase C, iota HUGO:PRKCI HGNC:9404 ENTREZ:5584 UNIPROT:P41743 GENECARDS:PRKCI REACTOME:58207 KEGG:5584 ATLASONC:PRKCIID41857ch3q26 WIKI:PRKCI protein kinase C, theta HUGO:PRKCQ HGNC:9410 ENTREZ:5588 UNIPROT:Q04759 GENECARDS:PRKCQ REACTOME:58217 KEGG:5588 ATLASONC:GC_PRKCQ WIKI:PRKCQ Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity. PMID:15567848 PMID:11313945 PMID:11940581 Only PKC alpha and delta PMID:21386996 References_end</body> </html> Identifiers_begin: protein kinase C alpha PKCA HUGO:PRKCA HGNC:9393 ENTREZ:5578 UNIPROT:P17252 GENECARDS:PRKCA REACTOME:58197 KEGG:5578 ATLASONC:GC_PRKCA WIKI:PRKCA protein kinase C beta PKCB PRKCB1 PRKCB2 "protein kinase C beta 1" HUGO:PRKCB HGNC:9395 ENTREZ:5579 UNIPROT:P05771 GENECARDS:PRKCB REACTOME:58199 KEGG:5579 ATLASONC:GC_PRKCB WIKI:PRKCB protein kinase C gamma PKCG SCA14 HUGO:PRKCG HGNC:9402 ENTREZ:5582 UNIPROT:P05129 GENECARDS:PRKCG REACTOME:58205 KEGG:5582 ATLASONC:GC_PRKCG WIKI:PRKCG protein kinase C, delta HUGO:PRKCD HGNC:9399 ENTREZ:5580 UNIPROT:Q05655 GENECARDS:PRKCD REACTOME:58201 KEGG:5580 ATLASONC:PRKCDID42901ch3p21 WIKI:PRKCD protein kinase C, epsilon HUGO:PRKCE HGNC:9401 ENTREZ:5581 UNIPROT:Q02156 GENECARDS:PRKCE REACTOME:58203 KEGG:5581 ATLASONC:GC_PRKCE WIKI:PRKCE protein kinase C, eta HUGO:PRKCH HGNC:9403 ENTREZ:5583 UNIPROT:P24723 GENECARDS:PRKCH REACTOME:58209 KEGG:5583 ATLASONC:GC_PRKCH WIKI:PRKCH protein kinase C, iota HUGO:PRKCI HGNC:9404 ENTREZ:5584 UNIPROT:P41743 GENECARDS:PRKCI REACTOME:58207 KEGG:5584 ATLASONC:PRKCIID41857ch3q26 WIKI:PRKCI protein kinase C, theta HUGO:PRKCQ HGNC:9410 ENTREZ:5588 UNIPROT:Q04759 GENECARDS:PRKCQ REACTOME:58217 KEGG:5588 ATLASONC:GC_PRKCQ WIKI:PRKCQ Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity. PMID:15567848 PMID:11313945 PMID:11940581 Only PKC alpha and delta PMID:21386996 References_end</body> </html> </notes> <label text="PKC*"/> <bbox w="50.0" h="25.0" x="610.0" y="1418.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s993_mpk1_mpk1_csa4" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:GRB2:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:GRB2:RAS*:RTK*:SOS*"/> <bbox w="189.0" h="103.0" x="1430.0" y="1437.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s61_mpk1_mpk1_sa38"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1555.5" y="1469.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s756_mpk1_mpk1_sa39"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1555.5" y="1493.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s143_mpk1_mpk1_sa49"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1446.5" y="1493.5"/> <glyph class="state variable" id="_9bedcf35-09ed-4d1b-aa2a-0cf26a648f40"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1439.0" y="1501.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s823_mpk1_mpk1_sa586"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1557.0" y="1448.0"/> <glyph class="state variable" id="_e1483822-40ad-4819-bf37-b1f63828f79c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1602.0" y="1460.6776"/> </glyph> <glyph class="state variable" id="_9cd1ec45-d732-4215-a82a-5e0d6e799fda"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1602.0" y="1460.6776"/> </glyph> <glyph class="state variable" id="_70bd4e99-44f8-405b-a22b-a1a85ecb75f0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1602.0" y="1455.5"/> </glyph> <glyph class="unit of information" id="_4f842124-f862-444c-ba7f-c1b399bb8e64"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1559.5" y="1443.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s857_mpk1_mpk1_sa618"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1508.375" y="1493.0"/> <glyph class="state variable" id="_a7a5fb16-7a5b-49b4-aa91-e59196915259"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1500.875" y="1500.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s995_mpk1_mpk1_csa11" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:GRB2:KSR1:MEK*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:GRB2:KSR1:MEK*:RAS*:RTK*:SOS*"/> <bbox w="259.0" h="168.0" x="1806.5" y="1405.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s86_mpk1_mpk1_sa56"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1974.0" y="1437.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s87_mpk1_mpk1_sa57"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1974.0" y="1462.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s82_mpk1_mpk1_sa62"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="41.0" h="77.0" x="1826.5" y="1463.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s83_mpk1_mpk1_sa63"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="1871.5" y="1488.0"/> <glyph class="state variable" id="_abc450e2-ee67-48c0-9912-6d8545dcde37"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1864.0" y="1500.333"/> </glyph> <glyph class="state variable" id="_79bea096-e819-4da9-873d-201e234cdea1"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1864.0" y="1491.451"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s144_mpk1_mpk1_sa59"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1867.0" y="1463.0"/> <glyph class="state variable" id="_5932bf57-ff63-48bb-9c7e-5df3d0902257"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1859.5" y="1471.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s825_mpk1_mpk1_sa584"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1975.0" y="1416.0"/> <glyph class="state variable" id="_d425768b-9be7-4aec-adf4-013788532af8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2020.0" y="1428.6776"/> </glyph> <glyph class="state variable" id="_ab211c4d-a630-4aec-a65d-b71f826fd305"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2020.0" y="1428.6776"/> </glyph> <glyph class="state variable" id="_7da58891-5b76-4396-adc6-ead8450a9179"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2020.0" y="1423.5"/> </glyph> <glyph class="unit of information" id="_971f89c4-7241-492d-9d1f-906c789725db"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1977.5" y="1411.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s88_mpk1_mpk1_sa620"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1926.125" y="1462.0"/> <glyph class="state variable" id="_5b353ab0-9077-4806-8409-e138c58ce5e6"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1918.625" y="1469.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s996_mpk1_mpk1_csa24" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:GRB2:KSR1-NTER*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:GRB2:KSR1-NTER*:RAS*:RTK*:SOS*"/> <bbox w="257.0" h="135.0" x="1830.0" y="1614.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s207_mpk1_mpk1_sa125"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="2006.5" y="1645.125"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s210_mpk1_mpk1_sa126"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="2005.5" y="1669.125"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s209_mpk1_mpk1_sa128"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1893.5" y="1669.875"/> <glyph class="state variable" id="_af14ec19-7cbe-4e2b-9625-fd300f45e879"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1886.0" y="1677.875"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s211_mpk1_mpk1_sa130"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is cleaved by CASPASE3 in two regions: the C-ter region which mediates MEK binding and the N-ter region which contains the ERK binding site and the C1 domain required for plasma membrane localisation PMID:17613518 References_end</body> </html> </notes> <label text="KSR1-NTER*"/> <bbox w="116.0" h="25.0" x="1885.0" y="1695.0"/> <glyph class="unit of information" id="_47efb3d3-baaa-4d68-abb4-bb60a5afaa5a"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="1918.0" y="1690.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s827_mpk1_mpk1_sa588"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="2007.1818" y="1624.0"/> <glyph class="state variable" id="_8f57c748-f60a-46b0-bcc4-e600fcca032c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2052.1816" y="1636.6776"/> </glyph> <glyph class="state variable" id="_f76d2919-7819-4940-8637-faeeb6620aca"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2052.1816" y="1636.6776"/> </glyph> <glyph class="state variable" id="_7fe8939b-d1c9-407c-85b0-908adfd6cb78"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2052.1816" y="1631.5"/> </glyph> <glyph class="unit of information" id="_d5580ccc-5268-4519-8c33-bcc0dbd648a5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2009.6818" y="1619.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s208_mpk1_mpk1_sa632"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1957.125" y="1669.5"/> <glyph class="state variable" id="_ace4bd27-f7d3-4f6d-b751-b2d5a8d706a4"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1949.625" y="1677.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s994_mpk1_mpk1_csa12" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:ERK*:GRB2:KSR1:MEK*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:ERK*:GRB2:KSR1:MEK*:RAS*:RTK*:SOS*"/> <bbox w="286.0" h="163.0" x="1391.5" y="1600.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s866_mpk1_mpk1_sa621"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1591.625" y="1608.0"/> <glyph class="state variable" id="_9eff1389-7070-40bb-bbee-9b29ec90989b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1636.625" y="1620.6776"/> </glyph> <glyph class="state variable" id="_88988dbc-7411-4748-af35-01493b032f9e"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1636.625" y="1620.6776"/> </glyph> <glyph class="state variable" id="_8ac615fe-2e98-44cd-8b03-184bc1504d1a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1636.625" y="1615.5"/> </glyph> <glyph class="unit of information" id="_46b80b94-be1e-4f6e-8ba0-d51c4dac3fdc"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1594.125" y="1603.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s860_mpk1_mpk1_sa622"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1590.625" y="1629.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s861_mpk1_mpk1_sa623"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1590.625" y="1654.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s865_mpk1_mpk1_sa627"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="41.0" h="77.0" x="1443.125" y="1655.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s867_mpk1_mpk1_sa628"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="66.0" h="26.0" x="1488.0" y="1705.75"/> <glyph class="state variable" id="_a40a3458-dea0-461e-af26-2d038a7c9c90"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.5" y="1718.2809"/> </glyph> <glyph class="state variable" id="_0e5a3efa-d8d2-4a10-9392-ba5a2c6ff1d4"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.5" y="1708.6022"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s868_mpk1_mpk1_sa629"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="1487.625" y="1681.25"/> <glyph class="state variable" id="_b79f96fb-47f0-4f08-8c54-e86fa9ab1874"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.125" y="1693.583"/> </glyph> <glyph class="state variable" id="_de176abb-e7f6-4110-9dd6-f1030fedd7b3"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.125" y="1684.701"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s869_mpk1_mpk1_sa630"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1483.125" y="1656.25"/> <glyph class="state variable" id="_98f6f7ea-b30e-482d-a29d-f977db63ba9a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1475.625" y="1664.25"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s870_mpk1_mpk1_sa631"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1542.125" y="1655.0"/> <glyph class="state variable" id="_5742a898-0591-45a3-927a-56e12b3caf4e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1534.625" y="1662.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s953_mpk1_mpk1_csa112" compartmentRef="mpk1_mpk1_c7_mpk1_mpk1_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BAD:BCL2 Identifiers_end</body> </html> </notes> <label text="BAD:BCL2"/> <bbox w="80.0" h="85.0" x="1177.0" y="1867.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s954_mpk1_mpk1_sa703"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: BCL2-associated agonist of cell death HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release. PMID:12107820 References_end Identifiers_begin: BCL2-associated agonist of cell death HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 GENECARDS:BAD REACTOME:50663 KEGG:572 ATLASONC:BADID130ch11q13 WIKI:BAD Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:APOPTOSIS_GENES MAP:apoptosis / MODULE:MITOCH_METABOLISM MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release. PMID:12107820 PMID:10949026 PMID:19641503 References_end</body> </html> Identifiers_begin: BCL2-associated agonist of cell death HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 GENECARDS:BAD REACTOME:50663 KEGG:572 ATLASONC:BADID130ch11q13 WIKI:BAD Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:APOPTOSIS_GENES MAP:apoptosis / MODULE:MITOCH_METABOLISM MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release. PMID:12107820 PMID:10949026 PMID:19641503 References_end</body> </html> </notes> <label text="BAD"/> <bbox w="50.0" h="25.0" x="1192.0" y="1879.5"/> <glyph class="state variable" id="_ac8f8ca4-2f77-417a-a3e5-65d262dd8b2e"> <state value="" variable="S112"/> <bbox w="30.0" h="10.0" x="1177.3079" y="1874.5"/> </glyph> <glyph class="state variable" id="_1340fb6c-6c64-4df8-9710-b16632532553"> <state value="" variable="S136"/> <bbox w="30.0" h="10.0" x="1227.0" y="1874.6343"/> </glyph> <glyph class="state variable" id="_8a29a6f6-0f50-438a-910f-6e8c3987ab10"> <state value="" variable="S155"/> <bbox w="30.0" h="10.0" x="1226.6136" y="1899.5"/> </glyph> <glyph class="state variable" id="_d042000c-3238-4732-91df-9140505db329"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1187.0" y="1887.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s955_mpk1_mpk1_sa704"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: B-cell CLL/lymphoma 2 HUGO:BCL2 HGNC:990 ENTREZ:596 UNIPROT:P10415 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: BCL2 protein can target Raf-1 (C-Raf) to mitochondria. PMID:8929532 References_end</body> </html> </notes> <label text="BCL2"/> <bbox w="50.0" h="25.0" x="1192.0" y="1904.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s978_mpk1_mpk1_csa60" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MEK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="MEK*:β-Arrestin2*"/> <bbox w="115.0" h="119.0" x="2683.0" y="1881.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s513_mpk1_mpk1_sa292"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="76.0" x="2746.0" y="1889.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s514_mpk1_mpk1_sa293"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2698.0" y="1918.0"/> <glyph class="state variable" id="_a373f1f1-41b6-48e1-93e2-01c516601b97"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2693.0" y="1929.6664"/> </glyph> <glyph class="state variable" id="_4123112a-e14e-46b7-945d-4198d39c8cd8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2693.0" y="1921.1261"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s998_mpk1_mpk1_csa46" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GPCR*:GRK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="GPCR*:GRK*:β-Arrestin2*"/> <bbox w="129.0" h="159.0" x="2228.0" y="1560.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s480_mpk1_mpk1_sa237"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="76.0" x="2269.0" y="1618.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s537_mpk1_mpk1_sa312"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2268.5" y="1591.3334"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s828_mpk1_mpk1_sa591"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="66.0" h="26.0" x="2260.0908" y="1568.0"/> <glyph class="state variable" id="_5ae55e27-8411-4a2b-ae2f-91e00b07429a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2252.5908" y="1576.0"/> </glyph> <glyph class="unit of information" id="_06657ec5-5cdc-4f32-b485-4668262f0d15"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2270.5908" y="1563.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s984_mpk1_mpk1_csa66" compartmentRef="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:β-Arrestin2*"/> <bbox w="146.0" h="119.0" x="2299.0" y="2122.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s550_mpk1_mpk1_sa319"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="77.0" x="2375.5" y="2132.3333"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s551_mpk1_mpk1_sa320"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2326.5" y="2161.3333"/> <glyph class="state variable" id="_d5cba11a-e3aa-41b0-af2b-0bae5c1cfe7e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2172.9995"/> </glyph> <glyph class="state variable" id="_a9151b7d-5061-4283-a57c-47e7f1b49638"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2164.4592"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s552_mpk1_mpk1_sa321"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2326.5" y="2186.3333"/> <glyph class="state variable" id="_efcef904-7f4f-4261-b434-4d30a5352f99"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2198.19"/> </glyph> <glyph class="state variable" id="_539630c2-0764-42cb-81bd-cef35d8384ea"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2188.8833"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s985_mpk1_mpk1_csa67" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:β-Arrestin2*"/> <bbox w="140.0" h="116.0" x="2389.0" y="2306.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s803_mpk1_mpk1_sa560"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="77.0" x="2462.0" y="2314.2727"/> </glyph> <glyph class="macromolecule multimer" id="mpk1_mpk1_s804_mpk1_mpk1_sa561"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - ERK represents both ERK1 and ERK2 because it is not completely clear when the two isoforms behave differently. This also happens for the activation on late endosomes: it is known that only ERK1 is activated there, however when ERK1 reaches nucleus, it behaves like ERK2. - Once activated, ERK may either keep being in complex with its activators and scaffolds, or be released in the cytoplasm. In the latter case, it may either dimerise, being able to activate its cytoplasmic targets, or not, being able to translocate to the nucleus. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2414.75" y="2369.7727"/> <glyph class="unit of information" id="_caba5678-c407-4e95-bf44-304415875034"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="2429.75" y="2364.7727"/> </glyph> <glyph class="state variable" id="_4e553ef9-0580-43b2-8c30-331c0dcbe10a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2407.25" y="2381.6294"/> </glyph> <glyph class="state variable" id="_1685e26d-bb19-4a32-8141-4904dc394645"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2407.25" y="2372.3228"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s805_mpk1_mpk1_sa563"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2413.0417" y="2342.3862"/> <glyph class="state variable" id="_a23a6b35-fd8f-4413-803b-0befbeccc5a8"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2405.5417" y="2354.0525"/> </glyph> <glyph class="state variable" id="_b9dd0927-8266-4096-80c7-8d84540ee1ce"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2405.5417" y="2345.5122"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1002_mpk1_mpk1_csa37" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RAS*:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RAS*:RASGRP1"/> <bbox w="181.0" h="110.0" x="187.5" y="2281.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s483_mpk1_mpk1_sa195"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="251.0" y="2316.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s485_mpk1_mpk1_sa197"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="267.0" y="2341.5"/> <glyph class="state variable" id="_f46703b5-214a-4029-99b4-da2e3c29cb62"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="259.5" y="2349.0"/> </glyph> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s489_mpk1_mpk1_sa276"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="203.44444" y="2299.2222"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s842_mpk1_mpk1_sa602"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: DAG Identifiers_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="249.125" y="2292.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1003_mpk1_mpk1_csa38" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RAF1:RAS*:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RAF1:RAS*:RASGRP1"/> <bbox w="226.0" h="90.0" x="176.0" y="2525.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s321_mpk1_mpk1_sa206"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="243.5" y="2561.0"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s490_mpk1_mpk1_sa277"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="195.44444" y="2543.2222"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s320_mpk1_mpk1_sa601"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Generic_begin: DAG Generic_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="239.125" y="2537.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s843_mpk1_mpk1_sa603"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="311.375" y="2537.0"/> <glyph class="state variable" id="_74e30b57-ae43-435e-82f3-bfb5a6f1e544"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="303.875" y="2544.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s844_mpk1_mpk1_sa604"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="309.375" y="2563.0"/> <glyph class="state variable" id="_95c288a1-a3ee-4469-8b75-f8f20eb3c62d"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="301.875" y="2571.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1004_mpk1_mpk1_csa41" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:SEF*"/> <bbox w="112.0" h="87.0" x="425.0" y="2436.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s339_mpk1_mpk1_sa217"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="50.0" h="25.0" x="436.875" y="2446.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s340_mpk1_mpk1_sa215"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="474.26135" y="2446.1592"/> <glyph class="state variable" id="_7b125ca8-26a3-491d-97a3-4024fa4013b9"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.26135" y="2457.8254"/> </glyph> <glyph class="state variable" id="_c6d7a1f4-22c4-42ac-9b8b-24fc7248c93a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.26135" y="2449.2852"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s346_mpk1_mpk1_sa224"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="474.875" y="2471.75"/> <glyph class="state variable" id="_5f5a6d29-7887-4971-903a-c959036db6d7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.875" y="2483.6067"/> </glyph> <glyph class="state variable" id="_ac4e32fe-5748-49f9-acdd-d4ea5a60fba0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.875" y="2474.3"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1005_mpk1_mpk1_csa43" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:SEF*"/> <bbox w="126.0" h="87.0" x="677.0" y="2436.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s343_mpk1_mpk1_sa221"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="50.0" h="25.0" x="693.875" y="2445.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s344_mpk1_mpk1_sa222"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="730.26135" y="2445.6592"/> <glyph class="state variable" id="_0387c67c-4095-480e-8220-11ab5beb7304"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="722.76135" y="2457.3254"/> </glyph> <glyph class="state variable" id="_f9bfd5a4-8698-42ae-a0e2-8d42e1f7bdd6"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="722.76135" y="2448.7852"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s345_mpk1_mpk1_sa223"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="728.98865" y="2471.8408"/> <glyph class="state variable" id="_d11b153a-c373-48bb-a1e7-5111f4343efc"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="721.48865" y="2483.6975"/> </glyph> <glyph class="state variable" id="_d5846865-16d6-4d0b-8005-0ff2fd7720d5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="721.48865" y="2474.3909"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1006_mpk1_mpk1_csa63" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:SEF*"/> <bbox w="126.0" h="89.0" x="697.0" y="2565.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s533_mpk1_mpk1_sa308"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="66.0" h="26.0" x="717.5" y="2575.8335"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s534_mpk1_mpk1_sa309"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="753.5" y="2577.8335"/> <glyph class="state variable" id="_af469740-e1e1-4791-8034-45b4ea5811d0"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.0" y="2590.1665"/> </glyph> <glyph class="state variable" id="_48e30b55-e367-4de8-b272-0ea8ecdcb26e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.0" y="2581.2847"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="mpk1_mpk1_s535_mpk1_mpk1_sa310"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - ERK represents both ERK1 and ERK2 because it is not completely clear when the two isoforms behave differently. This also happens for the activation on late endosomes: it is known that only ERK1 is activated there, however when ERK1 reaches nucleus, it behaves like ERK2. - Once activated, ERK may either keep being in complex with its activators and scaffolds, or be released in the cytoplasm. In the latter case, it may either dimerise, being able to activate its cytoplasmic targets, or not, being able to translocate to the nucleus. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="66.0" h="26.0" x="753.9167" y="2603.3335"/> <glyph class="unit of information" id="_2233a7b4-a468-4b92-8594-550d194c07f6"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="776.9167" y="2598.3335"/> </glyph> <glyph class="state variable" id="_10000386-760f-4a04-8f59-e8d7690e1590"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.4167" y="2615.8645"/> </glyph> <glyph class="state variable" id="_8b1ea434-92e9-4659-9e6c-f47562f7afe8"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.4167" y="2606.1855"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1007_mpk1_mpk1_csa58" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="MEK*:SEF*"/> <bbox w="104.0" h="93.0" x="633.0" y="2157.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s802_mpk1_mpk1_sa558"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="37.0" h="58.0" x="640.2727" y="2168.318"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s855_mpk1_mpk1_sa617"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="37.0" h="58.0" x="678.625" y="2168.0"/> <glyph class="state variable" id="_e88b8d87-7898-4a5a-9481-405d4e58e863"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="673.625" y="2201.666"/> </glyph> <glyph class="state variable" id="_e3093863-b16a-4bb9-a59e-ba894a1cb120"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="673.625" y="2181.8525"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1008_mpk1_mpk1_csa113" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GAB1:GRB2 Identifiers_end</body> </html> </notes> <label text="GAB1:GRB2"/> <bbox w="80.0" h="84.0" x="706.5" y="1997.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s970_mpk1_mpk1_sa713"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="725.5" y="2005.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s971_mpk1_mpk1_sa714"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 GENECARDS:GAB1 REACTOME:147726 ATLASONC:GC_GAB1 WIKI:GAB1 GRB2-associated binding protein 2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:11313945 PMID:11940581 References_end</body> </html> </notes> <label text="GAB1"/> <bbox w="50.0" h="25.0" x="725.5" y="2030.5"/> <glyph class="state variable" id="_8d860e18-294b-4d55-9bfe-2cc5ac05ace1"> <state value="" variable="Y977"/> <bbox w="30.0" h="10.0" x="710.8078" y="2025.5"/> </glyph> <glyph class="state variable" id="_9b795641-6ebf-4850-9e34-3d23151a0b7d"> <state value="" variable="Y989"/> <bbox w="30.0" h="10.0" x="760.5" y="2025.6343"/> </glyph> <glyph class="state variable" id="_412cad16-c048-4108-9f3f-4393ca23ba42"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="718.0" y="2038.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1009_mpk1_mpk1_csa21" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:SOS*"/> <bbox w="75.0" h="84.0" x="620.5" y="1842.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s35_mpk1_mpk1_sa23"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="633.5" y="1852.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s762_mpk1_mpk1_sa25"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="633.5" y="1877.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1010_mpk1_mpk1_csa111" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GAB1:GRB2 Identifiers_end</body> </html> </notes> <label text="GAB1:GRB2"/> <bbox w="80.0" h="84.0" x="897.0" y="1832.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s967_mpk1_mpk1_sa693"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="916.0" y="1840.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s968_mpk1_mpk1_sa694"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 GENECARDS:GAB1 REACTOME:147726 ATLASONC:GC_GAB1 WIKI:GAB1 GRB2-associated binding protein 2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:11313945 PMID:11940581 References_end</body> </html> </notes> <label text="GAB1"/> <bbox w="50.0" h="25.0" x="916.0" y="1865.5"/> <glyph class="state variable" id="_9f0f0886-9e42-4296-9742-6091ecd466c0"> <state value="" variable="Y977"/> <bbox w="30.0" h="10.0" x="901.3078" y="1860.5"/> </glyph> <glyph class="state variable" id="_6f8e484a-dd6a-4e7f-a380-90f489765ded"> <state value="" variable="Y989"/> <bbox w="30.0" h="10.0" x="951.0" y="1860.6343"/> </glyph> <glyph class="state variable" id="_94a016a3-2efc-4739-b377-2fa9c6ae3bf0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="911.0" y="1873.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1011_mpk1_mpk1_csa14" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:LAMTOR2:MP1* Identifiers_end</body> </html> </notes> <label text="LAMTOR2:MP1*"/> <bbox w="119.0" h="98.0" x="1223.0" y="2254.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s118_mpk1_mpk1_sa73"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="50.0" h="25.0" x="1233.0" y="2264.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s923_mpk1_mpk1_sa74"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="66.0" h="26.0" x="1266.0" y="2284.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1012_mpk1_mpk1_csa15" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:LAMTOR2:MEK*:MP1* Identifiers_end</body> </html> </notes> <label text="LAMTOR2:MEK*:MP1*"/> <bbox w="158.0" h="99.0" x="1207.0" y="2371.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s392_mpk1_mpk1_sa265"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1223.8334" y="2401.1665"/> <glyph class="state variable" id="_2860d97b-a2c6-4c0d-833c-01b30d4c3e5c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1218.8334" y="2412.8328"/> </glyph> <glyph class="state variable" id="_6fc655ea-5710-4125-844d-4cf3348401f1"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1218.8334" y="2404.2925"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s854_mpk1_mpk1_sa615"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="33.0" h="66.0" x="1270.875" y="2380.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s853_mpk1_mpk1_sa616"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="56.125" h="27.5" x="1303.875" y="2399.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1013_mpk1_mpk1_csa16" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:LAMTOR2:MEK*:MP1*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:LAMTOR2:MEK*:MP1*:RAS*:RTK*:SOS*"/> <bbox w="276.0" h="152.0" x="906.0" y="2248.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s123_mpk1_mpk1_sa83"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1079.5" y="2282.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s124_mpk1_mpk1_sa84"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1080.5" y="2307.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s128_mpk1_mpk1_sa86"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="64.25" h="23.5" x="1037.75" y="2334.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s126_mpk1_mpk1_sa87"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="50.0" h="25.0" x="995.0" y="2287.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s393_mpk1_mpk1_sa266"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="954.5" y="2330.1665"/> <glyph class="state variable" id="_b8f96bde-a663-4375-8860-977bbaf55444"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="949.5" y="2341.8328"/> </glyph> <glyph class="state variable" id="_79eb56d0-014f-4cf1-be31-88903af728ee"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="949.5" y="2333.2925"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s817_mpk1_mpk1_sa579"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1079.8181" y="2260.4546"/> <glyph class="state variable" id="_ec560b87-bb25-4ef6-9d8c-f3c41a955c1a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1124.8181" y="2273.1323"/> </glyph> <glyph class="state variable" id="_9ef2ad7b-cb09-4e9b-abad-5c6965516ac3"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1124.8181" y="2273.1323"/> </glyph> <glyph class="state variable" id="_e5cf7d46-2d20-4f79-96a8-0f2cde457225"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1124.8181" y="2267.9546"/> </glyph> <glyph class="unit of information" id="_d6ba358f-6aa6-4cd9-aa93-454b36bbd6e3"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1082.3181" y="2255.4546"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s845_mpk1_mpk1_sa605"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1037.125" y="2307.0"/> <glyph class="state variable" id="_dedc3310-3661-43ac-bed6-714b7660f9aa"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1029.625" y="2314.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1014_mpk1_mpk1_csa18" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS*"/> <bbox w="312.0" h="146.0" x="904.5" y="2537.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s160_mpk1_mpk1_sa101"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="969.5" y="2591.5"/> <glyph class="state variable" id="_b0ac8615-9c96-4cf6-9b3e-2eb6bed79906"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="962.0" y="2599.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s396_mpk1_mpk1_sa267"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="970.5" y="2616.8335"/> <glyph class="state variable" id="_c001f9ce-0698-44eb-abc3-2b2e9e9be700"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="963.0" y="2629.1665"/> </glyph> <glyph class="state variable" id="_aff9846e-c6a0-4517-879a-91d3e243a3bd"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="963.0" y="2620.2847"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s846_mpk1_mpk1_sa606"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1095.4432" y="2545.9773"/> <glyph class="state variable" id="_d78f204c-63ea-40bc-a3ab-4defc482eea7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1140.4432" y="2558.655"/> </glyph> <glyph class="state variable" id="_20002ee2-2ddd-4ae9-b279-f7c458a1f221"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1140.4432" y="2558.655"/> </glyph> <glyph class="state variable" id="_c0a5d43b-a167-4e8e-b438-c5d279811394"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1140.4432" y="2553.4773"/> </glyph> <glyph class="unit of information" id="_b8d1baa1-af7e-4335-873d-6aa70158fa15"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1097.9432" y="2540.9773"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s847_mpk1_mpk1_sa607"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1095.125" y="2568.2727"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s848_mpk1_mpk1_sa608"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1096.125" y="2593.2727"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s850_mpk1_mpk1_sa610"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="58.625" h="25.977272" x="1053.375" y="2618.0227"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s851_mpk1_mpk1_sa611"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="66.0" h="26.0" x="1017.0" y="2567.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s849_mpk1_mpk1_sa613"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1055.125" y="2593.0"/> <glyph class="state variable" id="_a324d211-e878-41fa-899b-7d754adbfa15"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1047.625" y="2600.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1015_mpk1_mpk1_csa19" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="ERK*:GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS*"/> <bbox w="346.0" h="153.0" x="1229.75" y="2532.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s164_mpk1_mpk1_sa103"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1436.25" y="2564.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s165_mpk1_mpk1_sa104"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1436.25" y="2589.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s167_mpk1_mpk1_sa106"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="65.5" h="29.0" x="1388.5" y="2615.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s168_mpk1_mpk1_sa107"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="66.0" h="26.0" x="1357.0" y="2557.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s170_mpk1_mpk1_sa109"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="1305.75" y="2587.5"/> <glyph class="state variable" id="_b865870b-b3a5-4937-8d17-e5f254321b74"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1298.25" y="2595.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s385_mpk1_mpk1_sa258"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="66.0" h="26.0" x="1307.1666" y="2639.1665"/> <glyph class="state variable" id="_7ea11688-b7c4-4931-b724-5b8c4b660d12"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.6666" y="2651.6975"/> </glyph> <glyph class="state variable" id="_afd92290-7e5c-48f7-ae72-3de8957947fa"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.6666" y="2642.0186"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s399_mpk1_mpk1_sa268"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="1306.5" y="2613.1665"/> <glyph class="state variable" id="_7bc84657-eec5-4665-8772-307269305532"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.0" y="2625.4995"/> </glyph> <glyph class="state variable" id="_dcbd7163-732a-4070-b756-060e1ae70dd5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.0" y="2616.6177"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s819_mpk1_mpk1_sa581"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1437.8182" y="2541.0908"/> <glyph class="state variable" id="_874a35e0-26f6-46ac-beac-876ba0f6ee1d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1482.8182" y="2553.7686"/> </glyph> <glyph class="state variable" id="_3759715c-d311-4f0c-bb7f-514c500384bb"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1482.8182" y="2553.7686"/> </glyph> <glyph class="state variable" id="_9ba52174-529b-44fb-a4d5-670d4b92df51"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1482.8182" y="2548.5908"/> </glyph> <glyph class="unit of information" id="_3c843093-fbfe-4b96-9f9b-b09d8069efa4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1440.3182" y="2536.0908"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s852_mpk1_mpk1_sa614"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1387.875" y="2590.0"/> <glyph class="state variable" id="_6082744e-d388-4b9b-92a6-85bfd18195e2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1380.375" y="2597.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1016_mpk1_mpk1_csa71" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:GSK3_beta_*:RSK* Identifiers_end</body> </html> </notes> <label text="ERK*:GSK3β*:RSK*"/> <bbox w="111.0" h="106.0" x="1659.0" y="2631.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s763_mpk1_mpk1_sa352"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="1691.0" y="2637.4614"/> <glyph class="state variable" id="_505c64e5-5beb-4289-9591-334ecfa85dcb"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1683.5" y="2649.318"/> </glyph> <glyph class="state variable" id="_e465cdf6-7369-4c19-aa0d-f2b118edd04f"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1683.5" y="2640.0115"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s591_mpk1_mpk1_sa353"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 GENECARDS:GSK3B REACTOME:404223 ATLASONC:GSK3BID40761ch3q13 WIKI:GSK3B Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:cellcycle / MODULE:CYCLIND MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:12615961 PMID:20537194 glycogen synthase kinase 3 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end</body> </html> Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 GENECARDS:GSK3B REACTOME:404223 ATLASONC:GSK3BID40761ch3q13 WIKI:GSK3B Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:cellcycle / MODULE:CYCLIND MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:12615961 PMID:20537194 glycogen synthase kinase 3 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end</body> </html> Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 GENECARDS:GSK3B REACTOME:404223 ATLASONC:GSK3BID40761ch3q13 WIKI:GSK3B Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:cellcycle / MODULE:CYCLIND MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:12615961 PMID:20537194 glycogen synthase kinase 3 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end</body> </html> </notes> <label text="GSK3β*"/> <bbox w="63.0" h="27.0" x="1684.0" y="2663.4614"/> <glyph class="state variable" id="_f27163c0-ae57-44a5-a1d5-78586717c9b5"> <state value="" variable="S9"/> <bbox w="20.0" h="10.0" x="1674.3878" y="2658.4614"/> </glyph> <glyph class="state variable" id="_af273a5c-36c9-412b-a46b-2e827698d172"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1676.5" y="2671.9614"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s592_mpk1_mpk1_sa354"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - we group here all isoforms of RSK family, as we do not have enough information about the differencies in their behaviour ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: ribosomal protein S6 kinase 90kDa polypeptide 1 "ribosomal protein S6 kinase 90kD polypeptide 1" HUGO:RPS6KA1 HGNC:10430 ENTREZ:6195 UNIPROT:Q15418 ribosomal protein S6 kinase 90kDa polypeptide 2 "ribosomal protein S6 kinase 90kD polypeptide 2" HUGO:RPS6KA2 HGNC:10431 ENTREZ:6196 UNIPROT:Q15349 ribosomal protein S6 kinase 90kDa polypeptide 3 CLS "Coffin-Lowry syndrome" "mental retardation X-linked 19" MRX19 "ribosomal protein S6 kinase 90kD polypeptide 3" HUGO:RPS6KA3 HGNC:10432 ENTREZ:6197 UNIPROT:P51812 ribosomal protein S6 kinase 90kDa polypeptide 6 "ribosomal protein S6 kinase 90kD polypeptide 6" HUGO:RPS6KA6 HGNC:10435 ENTREZ:27330 UNIPROT:Q9UK32 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RSK2 is a well known ERK substrate in the cytoplasm. RSKs are exclusively activated by ERK. Activated RSK can be found in both nuclear and cytoplasmic compartments. PMID:15239952 PMID:15187187 References_end Identifiers_begin: ribosomal protein S6 kinase 90kDa polypeptide 1 "ribosomal protein S6 kinase 90kD polypeptide 1" HUGO:RPS6KA1 HGNC:10430 ENTREZ:6195 UNIPROT:Q15418 GENECARDS:RPS6KA1 REACTOME:57795 KEGG:6195 ATLASONC:RPS6KA1ID43477ch1p36 WIKI:RPS6KA1 ribosomal protein S6 kinase 90kDa polypeptide 2 "ribosomal protein S6 kinase 90kD polypeptide 2" HUGO:RPS6KA2 HGNC:10431 ENTREZ:6196 UNIPROT:Q15349 GENECARDS:RPS6KA2 REACTOME:57797 KEGG:6196 ATLASONC:GC_RPS6KA2 WIKI:RPS6KA2 ribosomal protein S6 kinase 90kDa polypeptide 3 CLS "Coffin-Lowry syndrome" "mental retardation X-linked 19" MRX19 "ribosomal protein S6 kinase 90kD polypeptide 3" HUGO:RPS6KA3 HGNC:10432 ENTREZ:6197 UNIPROT:P51812 GENECARDS:RPS6KA3 REACTOME:57799 KEGG:6197 ATLASONC:GC_RPS6KA3 WIKI:RPS6KA3 ribosomal protein S6 kinase 90kDa polypeptide 6 "ribosomal protein S6 kinase 90kD polypeptide 6" HUGO:RPS6KA6 HGNC:10435 ENTREZ:27330 UNIPROT:Q9UK32 GENECARDS:RPS6KA6 REACTOME:57801 KEGG:27330 ATLASONC:GC_RPS6KA6 WIKI:RPS6KA6 ribosomal protein S6 kinase 90kDa polypeptide 4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:PIM1 HGNC:8986 ENTREZ:5292 UNIPROT:P11309 GENECARDS:PIM1 KEGG:9361 ATLASONC:PIM1ID261 WIKI:PIM1 ribosomal protein S6 kinase, 90kDa, polypeptide 5 HUGO:RPS6KA5 HGNC:10434 ENTREZ:9252 UNIPROT:O75582 GENECARDS:RPS6KA5 REACTOME:93593 KEGG:9252 ATLASONC:GC_RPS6KA5 WIKI:RPS6KA5 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RSK2 is a well known ERK substrate in the cytoplasm. RSKs are exclusively activated by ERK. Activated RSK can be found in both nuclear and cytoplasmic compartments. PMID:15239952 PMID:15187187 PMID:16286006 PMID:21233202 References_end Identifiers_begin: ribosomal protein S6 kinase 90kDa polypeptide 1 "ribosomal protein S6 kinase 90kD polypeptide 1" HUGO:RPS6KA1 HGNC:10430 ENTREZ:6195 UNIPROT:Q15418 GENECARDS:RPS6KA1 REACTOME:57795 KEGG:6195 ATLASONC:RPS6KA1ID43477ch1p36 WIKI:RPS6KA1 ribosomal protein S6 kinase 90kDa polypeptide 2 "ribosomal protein S6 kinase 90kD polypeptide 2" HUGO:RPS6KA2 HGNC:10431 ENTREZ:6196 UNIPROT:Q15349 GENECARDS:RPS6KA2 REACTOME:57797 KEGG:6196 ATLASONC:GC_RPS6KA2 WIKI:RPS6KA2 ribosomal protein S6 kinase 90kDa polypeptide 3 CLS "Coffin-Lowry syndrome" "mental retardation X-linked 19" MRX19 "ribosomal protein S6 kinase 90kD polypeptide 3" HUGO:RPS6KA3 HGNC:10432 ENTREZ:6197 UNIPROT:P51812 GENECARDS:RPS6KA3 REACTOME:57799 KEGG:6197 ATLASONC:GC_RPS6KA3 WIKI:RPS6KA3 ribosomal protein S6 kinase 90kDa polypeptide 6 "ribosomal protein S6 kinase 90kD polypeptide 6" HUGO:RPS6KA6 HGNC:10435 ENTREZ:27330 UNIPROT:Q9UK32 GENECARDS:RPS6KA6 REACTOME:57801 KEGG:27330 ATLASONC:GC_RPS6KA6 WIKI:RPS6KA6 ribosomal protein S6 kinase 90kDa polypeptide 4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:PIM1 HGNC:8986 ENTREZ:5292 UNIPROT:P11309 GENECARDS:PIM1 KEGG:9361 ATLASONC:PIM1ID261 WIKI:PIM1 ribosomal protein S6 kinase, 90kDa, polypeptide 5 HUGO:RPS6KA5 HGNC:10434 ENTREZ:9252 UNIPROT:O75582 GENECARDS:RPS6KA5 REACTOME:93593 KEGG:9252 ATLASONC:GC_RPS6KA5 WIKI:RPS6KA5 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RSK2 is a well known ERK substrate in the cytoplasm. RSKs are exclusively activated by ERK. Activated RSK can be found in both nuclear and cytoplasmic compartments. PMID:15239952 PMID:15187187 PMID:16286006 PMID:21233202 References_end</body> </html> </notes> <label text="RSK*"/> <bbox w="50.0" h="25.0" x="1689.0" y="2689.4614"/> <glyph class="state variable" id="_4c94aa3a-a6f4-41df-9e97-deb54deff641"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1681.5" y="2696.9614"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1017_mpk1_mpk1_csa49" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP6:ERK* Identifiers_end</body> </html> </notes> <label text="DUSP6:ERK*"/> <bbox w="90.0" h="83.0" x="2093.0" y="2462.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s374_mpk1_mpk1_sa249"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 6 HUGO:DUSP6 HGNC:3072 ENTREZ:1848 UNIPROT:Q16828 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: DUSP6 may capture activated ERK2 dephosphorylate it and anchor the inactive kinase in the cytoplasm. PMID:17052211 References_end</body> </html> </notes> <label text="DUSP6"/> <bbox w="50.0" h="25.0" x="2107.5" y="2470.0"/> <glyph class="state variable" id="_f3462dee-695b-4d5d-8025-de32e9d1775f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2102.5" y="2477.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s373_mpk1_mpk1_sa250"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2115.5" y="2496.0"/> <glyph class="state variable" id="_a7432642-ca4a-4776-b66d-d2008e3c68e7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2110.5" y="2507.8567"/> </glyph> <glyph class="state variable" id="_7856273d-2743-4704-a655-2d31999bf830"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2110.5" y="2498.55"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1018_mpk1_mpk1_csa44" compartmentRef="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:GPCR*:GRK*:MEK*:RAF1:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="ERK*:GPCR*:GRK*:MEK*:RAF1:β-Arrestin2*"/> <bbox w="234.0" h="160.0" x="2468.0" y="2080.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s350_mpk1_mpk1_sa228"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="77.0" x="2600.0" y="2137.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s351_mpk1_mpk1_sa229"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="50.0" h="25.0" x="2537.0" y="2139.0"/> <glyph class="state variable" id="_f2ad30b3-1fd1-4905-bdfc-47f03c2f1263"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2529.5" y="2146.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s352_mpk1_mpk1_sa230"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2550.7273" y="2188.5908"/> <glyph class="state variable" id="_dcf2e27a-9238-4e1c-852a-0c44c0562515"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2543.2273" y="2200.4475"/> </glyph> <glyph class="state variable" id="_02400c85-64c9-4d74-bb0a-3fa1a2534691"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2543.2273" y="2191.1409"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s353_mpk1_mpk1_sa231"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2549.0" y="2164.4092"/> <glyph class="state variable" id="_00378b10-eb85-4479-96ff-bbbdc8320d55"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2541.5" y="2176.0754"/> </glyph> <glyph class="state variable" id="_0f22942c-a9f5-491b-bf62-7eee03a76b36"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2541.5" y="2167.5352"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s540_mpk1_mpk1_sa314"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2599.5" y="2111.3333"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s816_mpk1_mpk1_sa578"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="50.0" h="25.0" x="2601.5454" y="2088.9092"/> <glyph class="state variable" id="_3c359c73-8bb0-40b0-af54-e5efe1b51c36"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2596.5454" y="2096.4092"/> </glyph> <glyph class="unit of information" id="_075ce3f9-4e3a-49b8-adc0-4809e54d636b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2604.0454" y="2083.9092"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1019_mpk1_mpk1_csa70" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:LEF_TCF*:_beta_-Catenin* Identifiers_end</body> </html> </notes> <label text="LEF_TCF*:β-Catenin*"/> <bbox w="120.0" h="83.0" x="327.0" y="3024.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s765_mpk1_mpk1_sa350"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: catenin (cadherin-associated protein) beta 1 88kDa "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 References_end Identifiers_begin: Catenin (cadherin-associated protein) beta 1 88 kDa HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 GENECARDS:CTNNB1 REACTOME:53048 KEGG:1499 ATLASONC:CTNNB1ID71 WIKI:CTNNB1 "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB catenin (cadherin-associated protein) beta 1 armadillo, beta-catenin Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19619488 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 PMID:17143292 PMID:23343194 References_end</body> </html> Identifiers_begin: Catenin (cadherin-associated protein) beta 1 88 kDa HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 GENECARDS:CTNNB1 REACTOME:53048 KEGG:1499 ATLASONC:CTNNB1ID71 WIKI:CTNNB1 "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB catenin (cadherin-associated protein) beta 1 armadillo, beta-catenin Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19619488 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 PMID:17143292 PMID:23343194 References_end</body> </html> Identifiers_begin: Catenin (cadherin-associated protein) beta 1 88 kDa HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 GENECARDS:CTNNB1 REACTOME:53048 KEGG:1499 ATLASONC:CTNNB1ID71 WIKI:CTNNB1 "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB catenin (cadherin-associated protein) beta 1 armadillo, beta-catenin Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19619488 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 PMID:17143292 PMID:23343194 References_end</body> </html> </notes> <label text="β-Catenin*"/> <bbox w="72.0" h="26.0" x="351.6154" y="3035.2307"/> <glyph class="state variable" id="_d7137bf5-7489-408d-8b56-e48a1cfb793a"> <state value="" variable="S45"/> <bbox w="25.0" h="10.0" x="375.0294" y="3056.2307"/> </glyph> <glyph class="state variable" id="_a90e2c73-7a41-416d-b3a5-75ac9ed1fddc"> <state value="" variable="T41"/> <bbox w="25.0" h="10.0" x="410.559" y="3056.2307"/> </glyph> <glyph class="state variable" id="_96fb8abe-9b06-4850-b000-c9faad4b8af5"> <state value="" variable="S37"/> <bbox w="25.0" h="10.0" x="411.1154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_0e419f8f-344b-420e-8abc-c99f6b1614a1"> <state value="" variable="S33"/> <bbox w="25.0" h="10.0" x="375.14404" y="3030.2307"/> </glyph> <glyph class="state variable" id="_7e1d3e9c-457f-43e1-b0b7-29aaaa636b26"> <state value="" variable="K19"/> <bbox w="25.0" h="10.0" x="339.55865" y="3030.2307"/> </glyph> <glyph class="state variable" id="_85ce044f-b029-4119-b287-f074bca53d67"> <state value="" variable="K49"/> <bbox w="25.0" h="10.0" x="339.1154" y="3056.0503"/> </glyph> <glyph class="state variable" id="_1e0a5f30-ce05-4d78-87a2-abab3119686f"> <state value="" variable="Y142"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_aecb6839-ec1b-41db-9e60-cc76ab4b3d0e"> <state value="" variable="S552"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_a7687334-a049-4bc3-af3a-5fe0354d6977"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="346.6154" y="3043.2307"/> </glyph> <glyph class="state variable" id="_3a577fc6-10f2-46b3-8f9e-9e53c2809076"> <state value="" variable="K394"/> <bbox w="30.0" h="10.0" x="337.05865" y="3030.2307"/> </glyph> <glyph class="state variable" id="_652e5b54-48b7-4fe8-93f1-bd5cb972c09c"> <state value="" variable="Y654"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_ec69efeb-3d4e-4162-b74d-c43684484fa6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="346.6154" y="3037.846"/> </glyph> <glyph class="state variable" id="_4871881f-8424-46ac-9aa1-3ddb1ab73fa9"> <state value="" variable="S522"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_d410f72f-2a73-43a4-874c-e1375b557df9"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="346.6154" y="3043.2307"/> </glyph> <glyph class="state variable" id="_a68ca309-8e5d-4724-b1a6-cd92ea5a4725"> <state value="" variable="S675"/> <bbox w="30.0" h="10.0" x="408.059" y="3056.2307"/> </glyph> <glyph class="state variable" id="_c07cbd85-5352-44fb-9655-d6954d1ed2aa"> <state value="" variable="K345"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s766_mpk1_mpk1_sa351"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: lymphoid enhancer-binding factor 1 HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 transcription factor 7 (T-cell specific HMG-box) HUGO:TCF7 HGNC:11639 ENTREZ:6932 UNIPROT:P36402 transcription factor 7-like 1 (T-cell specific HMG-box) TCF3 HUGO:TCF7L1 HGNC:11640 ENTREZ:83439 UNIPROT:Q9HCS4 transcription factor 7-like 2 (T-cell specific HMG-box) TCF4 HUGO:TCF7L2 HGNC:11641 ENTREZ:6934 UNIPROT:Q9NQB0 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1) HUGO:PCBD2 HGNC:24474 ENTREZ:84105 UNIPROT:Q9H0N5 GENECARDS:PCBD2 KEGG:84105 WIKI:PCBD2 HNF1 homeobox A MODY3 TCF1 "transcription factor 1 hepatic; LF-B1 hepatic nuclear factor (HNF1) albumin proximal factor" HUGO:HNF1A HGNC:11621 ENTREZ:6927 UNIPROT:P20823 GENECARDS:HNF1A REACTOME:403244 KEGG:6927 ATLASONC:GC_HNF1A WIKI:HNF1A HNF1 homeobox B TCF2 "transcription factor 2 hepatic; LF-B3; variant hepatic nuclear factor" HUGO:HNF1B HGNC:11630 ENTREZ:6928 UNIPROT:P35680 GENECARDS:HNF1B REACTOME:403844 KEGG:6928 ATLASONC:GC_HNF1B WIKI:HNF1B transcription factor 3 HUGO:TCF3 HGNC:11633 ENTREZ:6929 UNIPROT:P15923 GENECARDS:TCF3 REACTOME:65901 KEGG:6929 ATLASONC:E2A WIKI:TCF3 transcription factor 4 HUGO:TCF4 HGNC:11634 ENTREZ:6925 UNIPROT:P15884 GENECARDS:TCF4 REACTOME:57613 KEGG:6925 ATLASONC:GC_TCF4 WIKI:TCF4 CCAAT/enhancer binding protein (C/EBP) beta TCF5 HUGO:CEBPB HGNC:1834 ENTREZ:1051 UNIPROT:P17676 GENECARDS:CEBPB REACTOME:51866 KEGG:1051 ATLASONC:GC_CEBPB WIKI:CEBPB transcription factor-like 5 (basic helix-loop-helix) HUGO:TCFL5 HGNC:11646 ENTREZ:10732 UNIPROT:Q9UL49 GENECARDS:TCFL5 KEGG:10732 WIKI:TCFL5 info transcription factor A mitochondrial HUGO:TFAM HGNC:11741 ENTREZ:7019 UNIPROT:Q00059 GENECARDS:TFAM REACTOME:65899 KEGG:7019 ATLASONC:GC_TFAM WIKI:TFAM transcription factor 7 (T-cell specific HMG-box) HUGO:TCF7 HGNC:11639 ENTREZ:6932 UNIPROT:P36402 GENECARDS:TCF7 KEGG:6932 ATLASONC:GC_TCF7 WIKI:TCF7 transcription factor 7-like 1 (T-cell specific HMG-box) HUGO:TCF7L1 HGNC:11640 ENTREZ:83439 UNIPROT:Q9HCS4 GENECARDS:TCF7L1 KEGG:83439 ATLASONC:GC_TCF7L1 WIKI:TCF7L1 transcription factor 7-like 2 (T-cell specific HMG-box) HUGO:TCF7L2 HGNC:11641 ENTREZ:6934 UNIPROT:Q9NQB0 GENECARDS:TCF7L2 REACTOME:65596 KEGG:6934 ATLASONC:GC_TCF7L2 WIKI:TCF7L2 zinc finger E-box binding homeobox 1 TCF8 HUGO:ZEB1 HGNC:11642 ENTREZ:6935 UNIPROT:P37275 GENECARDS:ZEB1 KEGG:6935 ATLASONC:GC_ZEB1 WIKI:ZEB1 GC-rich sequence DNA-binding factor 2 PREVIOUS SYMBOLS/ C2orf3 "chromosome 2 open reading frame 3" TCF9 "transcription factor 9 (binds GC-rich sequences)" HUGO:GCFC2 HGNC:1317 ENTREZ:6936 UNIPROT:P16383 GENECARDS:GCFC2 KEGG:6936 WIKI:GCFC2 lymphoid enhancer-binding factor 1 HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 GENECARDS:LEF1 KEGG:51176 ATLASONC:GC_LEF1 WIKI:LEF1 nuclear factor (erythroid-derived 2)-like 1 TCF11 HUGO:NFE2L1 HGNC:7781 ENTREZ:4779 UNIPROT:Q14494 GENECARDS:NFE2L1 KEGG:4779 ATLASONC:GC_NFE2L1 WIKI:NFE2L1 transcription factor 12 HUGO:TCF12 HGNC:11623 ENTREZ:6938 UNIPROT:Q99081 GENECARDS:TCF12 REACTOME:56728 KEGG:6938 ATLASONC:TCF12ID406 WIKI:TCF12 TEA domain family member 1 (SV40 transcriptional enhancer factor) AA "atrophia areata peripapillary chorioretinal degeneration" TCF13 HUGO:TEAD1 HGNC:11714 ENTREZ:7003 UNIPROT:P28347 GENECARDS:TEAD1 REACTOME:65831 KEGG:7003 ATLASONC:GC_TEAD1 WIKI:TEAD1 TEA domain family member 4 TCF13L1 HUGO:TEAD4 HGNC:11717 ENTREZ:7004 UNIPROT:Q15561 GENECARDS:TEAD4 REACTOME:65837 KEGG:7004 WIKI:TEAD4 hepatocyte nuclear factor 4 alpha MODY MODY1 TCF14 HUGO:HNF4A HGNC:5024 ENTREZ:3172 UNIPROT:P41235 GENECARDS:HNF4A REACTOME:211473 KEGG:3172 ATLASONC:GC_HNF4A WIKI:HNF4A transcription factor 15 (basic helix-loop-helix) HUGO:TCF15 HGNC:11627 ENTREZ:6939 UNIPROT:Q12870 GENECARDS:TCF15 KEGG:6939 ATLASONC:GC_TCF15 WIKI:TCF15 conserved helix-loop-helix ubiquitous kinase TCF16 HUGO:CHUK HGNC:1974 ENTREZ:1147 UNIPROT:O15111 GENECARDS:CHUK REACTOME:57214 KEGG:1147 ATLASONC:GC_CHUK WIKI:CHUK zinc finger protein 354A TCF17 HUGO:ZNF354A HGNC:11628 ENTREZ:6940 UNIPROT:O60765 GENECARDS:ZNF354A REACTOME:65741 KEGG:6940 WIKI:ZNF354A transcription factor 19 HUGO:TCF19 HGNC:11629 ENTREZ:6941 UNIPROT:Q9Y242 GENECARDS:TCF19 KEGG:6941 WIKI:TCF19 transcription factor 20 HUGO:TCF20 HGNC:11631 ENTREZ:6942 UNIPROT:Q9UGU0 GENECARDS:TCF20 KEGG:6942 WIKI:TCF20 transcription factor 21 HUGO:TCF21 HGNC:11632 ENTREZ:6943 UNIPROT:O43680 GENECARDS:TCF21 KEGG:6943 ATLASONC:GC_TCF21 WIKI:TCF21 transcription factor 23 HUGO:TCF23 HGNC:18602 ENTREZ:150921 UNIPROT:Q7RTU1 GENECARDS:TCF23 KEGG:150921 WIKI:TCF23 transcription factor 24 HUGO:TCF24 HGNC:32275 ENTREZ:100129654 UNIPROT:Q7RTU0 GENECARDS:TCF24 KEGG:100129654 WIKI:TCF24 transcription factor 25 HUGO:TCF25 HGNC:29181 ENTREZ:22980 UNIPROT:Q9BQ70 GENECARDS:TCF25 KEGG:22980 ATLASONC:GC_TCF25 WIKI:TCF25 TCF3 TCF4 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:19623618 PMID:19619488 HNF1 homeobox Phosphorylation sites specific for HIPK2 not known PMID:21285352 References_end</body> </html> Identifiers_begin: pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1) HUGO:PCBD2 HGNC:24474 ENTREZ:84105 UNIPROT:Q9H0N5 GENECARDS:PCBD2 KEGG:84105 WIKI:PCBD2 HNF1 homeobox A MODY3 TCF1 "transcription factor 1 hepatic; LF-B1 hepatic nuclear factor (HNF1) albumin proximal factor" HUGO:HNF1A HGNC:11621 ENTREZ:6927 UNIPROT:P20823 GENECARDS:HNF1A REACTOME:403244 KEGG:6927 ATLASONC:GC_HNF1A WIKI:HNF1A HNF1 homeobox B TCF2 "transcription factor 2 hepatic; LF-B3; variant hepatic nuclear factor" HUGO:HNF1B HGNC:11630 ENTREZ:6928 UNIPROT:P35680 GENECARDS:HNF1B REACTOME:403844 KEGG:6928 ATLASONC:GC_HNF1B WIKI:HNF1B transcription factor 3 HUGO:TCF3 HGNC:11633 ENTREZ:6929 UNIPROT:P15923 GENECARDS:TCF3 REACTOME:65901 KEGG:6929 ATLASONC:E2A WIKI:TCF3 transcription factor 4 HUGO:TCF4 HGNC:11634 ENTREZ:6925 UNIPROT:P15884 GENECARDS:TCF4 REACTOME:57613 KEGG:6925 ATLASONC:GC_TCF4 WIKI:TCF4 CCAAT/enhancer binding protein (C/EBP) beta TCF5 HUGO:CEBPB HGNC:1834 ENTREZ:1051 UNIPROT:P17676 GENECARDS:CEBPB REACTOME:51866 KEGG:1051 ATLASONC:GC_CEBPB WIKI:CEBPB transcription factor-like 5 (basic helix-loop-helix) HUGO:TCFL5 HGNC:11646 ENTREZ:10732 UNIPROT:Q9UL49 GENECARDS:TCFL5 KEGG:10732 WIKI:TCFL5 info transcription factor A mitochondrial HUGO:TFAM HGNC:11741 ENTREZ:7019 UNIPROT:Q00059 GENECARDS:TFAM REACTOME:65899 KEGG:7019 ATLASONC:GC_TFAM WIKI:TFAM transcription factor 7 (T-cell specific HMG-box) HUGO:TCF7 HGNC:11639 ENTREZ:6932 UNIPROT:P36402 GENECARDS:TCF7 KEGG:6932 ATLASONC:GC_TCF7 WIKI:TCF7 transcription factor 7-like 1 (T-cell specific HMG-box) HUGO:TCF7L1 HGNC:11640 ENTREZ:83439 UNIPROT:Q9HCS4 GENECARDS:TCF7L1 KEGG:83439 ATLASONC:GC_TCF7L1 WIKI:TCF7L1 transcription factor 7-like 2 (T-cell specific HMG-box) HUGO:TCF7L2 HGNC:11641 ENTREZ:6934 UNIPROT:Q9NQB0 GENECARDS:TCF7L2 REACTOME:65596 KEGG:6934 ATLASONC:GC_TCF7L2 WIKI:TCF7L2 zinc finger E-box binding homeobox 1 TCF8 HUGO:ZEB1 HGNC:11642 ENTREZ:6935 UNIPROT:P37275 GENECARDS:ZEB1 KEGG:6935 ATLASONC:GC_ZEB1 WIKI:ZEB1 GC-rich sequence DNA-binding factor 2 PREVIOUS SYMBOLS/ C2orf3 "chromosome 2 open reading frame 3" TCF9 "transcription factor 9 (binds GC-rich sequences)" HUGO:GCFC2 HGNC:1317 ENTREZ:6936 UNIPROT:P16383 GENECARDS:GCFC2 KEGG:6936 WIKI:GCFC2 lymphoid enhancer-binding factor 1 HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 GENECARDS:LEF1 KEGG:51176 ATLASONC:GC_LEF1 WIKI:LEF1 nuclear factor (erythroid-derived 2)-like 1 TCF11 HUGO:NFE2L1 HGNC:7781 ENTREZ:4779 UNIPROT:Q14494 GENECARDS:NFE2L1 KEGG:4779 ATLASONC:GC_NFE2L1 WIKI:NFE2L1 transcription factor 12 HUGO:TCF12 HGNC:11623 ENTREZ:6938 UNIPROT:Q99081 GENECARDS:TCF12 REACTOME:56728 KEGG:6938 ATLASONC:TCF12ID406 WIKI:TCF12 TEA domain family member 1 (SV40 transcriptional enhancer factor) AA "atrophia areata peripapillary chorioretinal degeneration" TCF13 HUGO:TEAD1 HGNC:11714 ENTREZ:7003 UNIPROT:P28347 GENECARDS:TEAD1 REACTOME:65831 KEGG:7003 ATLASONC:GC_TEAD1 WIKI:TEAD1 TEA domain family member 4 TCF13L1 HUGO:TEAD4 HGNC:11717 ENTREZ:7004 UNIPROT:Q15561 GENECARDS:TEAD4 REACTOME:65837 KEGG:7004 WIKI:TEAD4 hepatocyte nuclear factor 4 alpha MODY MODY1 TCF14 HUGO:HNF4A HGNC:5024 ENTREZ:3172 UNIPROT:P41235 GENECARDS:HNF4A REACTOME:211473 KEGG:3172 ATLASONC:GC_HNF4A WIKI:HNF4A transcription factor 15 (basic helix-loop-helix) HUGO:TCF15 HGNC:11627 ENTREZ:6939 UNIPROT:Q12870 GENECARDS:TCF15 KEGG:6939 ATLASONC:GC_TCF15 WIKI:TCF15 conserved helix-loop-helix ubiquitous kinase TCF16 HUGO:CHUK HGNC:1974 ENTREZ:1147 UNIPROT:O15111 GENECARDS:CHUK REACTOME:57214 KEGG:1147 ATLASONC:GC_CHUK WIKI:CHUK zinc finger protein 354A TCF17 HUGO:ZNF354A HGNC:11628 ENTREZ:6940 UNIPROT:O60765 GENECARDS:ZNF354A REACTOME:65741 KEGG:6940 WIKI:ZNF354A transcription factor 19 HUGO:TCF19 HGNC:11629 ENTREZ:6941 UNIPROT:Q9Y242 GENECARDS:TCF19 KEGG:6941 WIKI:TCF19 transcription factor 20 HUGO:TCF20 HGNC:11631 ENTREZ:6942 UNIPROT:Q9UGU0 GENECARDS:TCF20 KEGG:6942 WIKI:TCF20 transcription factor 21 HUGO:TCF21 HGNC:11632 ENTREZ:6943 UNIPROT:O43680 GENECARDS:TCF21 KEGG:6943 ATLASONC:GC_TCF21 WIKI:TCF21 transcription factor 23 HUGO:TCF23 HGNC:18602 ENTREZ:150921 UNIPROT:Q7RTU1 GENECARDS:TCF23 KEGG:150921 WIKI:TCF23 transcription factor 24 HUGO:TCF24 HGNC:32275 ENTREZ:100129654 UNIPROT:Q7RTU0 GENECARDS:TCF24 KEGG:100129654 WIKI:TCF24 transcription factor 25 HUGO:TCF25 HGNC:29181 ENTREZ:22980 UNIPROT:Q9BQ70 GENECARDS:TCF25 KEGG:22980 ATLASONC:GC_TCF25 WIKI:TCF25 TCF3 TCF4 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:19623618 PMID:19619488 HNF1 homeobox Phosphorylation sites specific for HIPK2 not known PMID:21285352 References_end</body> </html> </notes> <label text="LEF_TCF*"/> <bbox w="65.0" h="25.0" x="353.6154" y="3060.2307"/> <glyph class="state variable" id="_abecbc7d-dd98-44a4-8b71-6de5b2fc249c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="413.6154" y="3055.7795"/> </glyph> <glyph class="state variable" id="_6d139007-3f22-4b6f-a3d9-e498eecca29d"> <state value="" variable="S40"/> <bbox w="25.0" h="10.0" x="406.1154" y="3078.1145"/> </glyph> <glyph class="state variable" id="_c9936902-1249-4e37-9b0f-2dfcc1f208e4"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="413.6154" y="3067.7307"/> </glyph> <glyph class="state variable" id="_53c7ad06-2194-40ed-ad4d-d636ab48f615"> <state value="" variable="S166"/> <bbox w="30.0" h="10.0" x="339.01556" y="3055.2307"/> </glyph> <glyph class="state variable" id="_28b2d11b-eaab-4508-b459-ca3adbf426a2"> <state value="" variable="T155"/> <bbox w="30.0" h="10.0" x="338.6154" y="3080.0571"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1020_mpk1_mpk1_csa48" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP5:ERK* Identifiers_end</body> </html> </notes> <label text="DUSP5:ERK*"/> <bbox w="85.0" h="90.0" x="707.0" y="3061.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s366_mpk1_mpk1_sa244"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 5 HUGO:DUSP5 HGNC:3071 ENTREZ:1847 UNIPROT:Q16690 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: DUSP5 represents an inducible ERK-specific MKP and it functions as both a nuclear anchor and inactivator of ERK MODULE:MAPK in mammalian cells. PMID:17052211 References_end</body> </html> </notes> <label text="DUSP5"/> <bbox w="60.0" h="27.0" x="721.0" y="3074.0"/> <glyph class="state variable" id="_2b29b4c2-1683-4660-8036-f686202bc15c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="716.0" y="3082.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s370_mpk1_mpk1_sa247"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="60.0" h="27.0" x="726.5" y="3101.0"/> <glyph class="state variable" id="_d9b768e8-c030-457f-a8f3-918c2c78932e"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="721.5" y="3114.205"/> </glyph> <glyph class="state variable" id="_42dcdbfb-a134-4877-a7cd-c908241882dc"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="721.5" y="3104.154"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1024_mpk1_mpk1_csa106" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP1:JNK* Identifiers_end</body> </html> </notes> <label text="DUSP1:JNK*"/> <bbox w="105.0" h="86.0" x="2322.0" y="3025.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s792_mpk1_mpk1_sa547"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 1 PTPN10 HUGO:DUSP1 HGNC:3064 ENTREZ:1843 UNIPROT:P28562 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MKP-1 (DUSP1) preferentially inactivates JNK and P38. DUSP1 play its phosphatase role in the nucleus. PMID:19436832 PMID:17496916 References_end</body> </html> </notes> <label text="DUSP1"/> <bbox w="62.0" h="25.0" x="2344.2856" y="3033.8572"/> <glyph class="state variable" id="_250aacef-0ee8-4423-b639-92c8358ff9ac"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2339.2856" y="3041.3572"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s794_mpk1_mpk1_sa549"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 8 PRKM8 HUGO:MAPK8 HGNC:6881 ENTREZ:5599 UNIPROT:P45983 mitogen-activated protein kinase 9 PRKM9 HUGO:MAPK9 HGNC:6886 ENTREZ:5601 UNIPROT:P45984 mitogen-activated protein kinase 10 PRKM10 HUGO:MAPK10 HGNC:6872 ENTREZ:5602 UNIPROT:P53779 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: mitogen-activated protein kinase 8 PRKM8 HUGO:MAPK8 HGNC:6881 ENTREZ:5599 UNIPROT:P45983 GENECARDS:MAPK8 REACTOME:59293 KEGG:5599 ATLASONC:JNK1ID196 WIKI:MAPK8 mitogen-activated protein kinase 9 PRKM9 HUGO:MAPK9 HGNC:6886 ENTREZ:5601 UNIPROT:P45984 GENECARDS:MAPK9 REACTOME:59295 KEGG:5601 ATLASONC:JNK2ID426 WIKI:MAPK9 mitogen-activated protein kinase 10 PRKM10 HUGO:MAPK10 HGNC:6872 ENTREZ:5602 UNIPROT:P53779 GENECARDS:MAPK10 REACTOME:59297 KEGG:5602 ATLASONC:JNK3ID427 WIKI:MAPK10 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:apoptosis / MODULE:MOMP_REGULATION MAP:apoptosis / MODULE:TNF_RESPONSE MAP:dnarepair / MODULE:G2_M_CHECKPOINT MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="JNK*"/> <bbox w="62.0" h="25.0" x="2352.0" y="3059.8572"/> <glyph class="state variable" id="_4d8eba59-e5e9-40ad-b177-7da7e0b8b91f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2347.0" y="3072.1096"/> </glyph> <glyph class="state variable" id="_9d21b5ed-abba-48c4-998a-d9acc0d37d67"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2347.0" y="3062.6047"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1025_mpk1_mpk1_csa107" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP1:p38* Identifiers_end</body> </html> </notes> <label text="DUSP1:p38*"/> <bbox w="91.0" h="86.0" x="2865.0" y="3051.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s791_mpk1_mpk1_sa546"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 1 PTPN10 HUGO:DUSP1 HGNC:3064 ENTREZ:1843 UNIPROT:P28562 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MKP-1 (DUSP1) preferentially inactivates JNK and P38. DUSP1 play its phosphatase role in the nucleus. PMID:19436832 PMID:17496916 References_end</body> </html> </notes> <label text="DUSP1"/> <bbox w="62.0" h="25.0" x="2880.2856" y="3058.8572"/> <glyph class="state variable" id="_f4d7d3a2-93b8-421a-9186-90e0d39282ca"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2875.2856" y="3066.3572"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s793_mpk1_mpk1_sa548"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: mitogen-activated protein kinase 11 PRKM11 HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 mitogen-activated protein kinase 12 SAPK3 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 mitogen-activated protein kinase 13 PRKM13 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 mitogen-activated protein kinase 14 CSBP1 CSBP2 CSPB1 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: mitogen-activated protein kinase 11 PRKM11 HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 GENECARDS:MAPK11 REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11 mitogen-activated protein kinase 12 SAPK3 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 GENECARDS:MAPK12 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12 mitogen-activated protein kinase 13 PRKM13 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 GENECARDS:MAPK13 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13 mitogen-activated protein kinase 14 CSBP1 CSBP2 CSPB1 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 GENECARDS:MAPK14 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14 Mxi2 P38 "P38 MAP kinase" PRKM14 PRKM15 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> Identifiers_begin: mitogen-activated protein kinase 11 PRKM11 HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 GENECARDS:MAPK11 REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11 mitogen-activated protein kinase 12 SAPK3 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 GENECARDS:MAPK12 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12 mitogen-activated protein kinase 13 PRKM13 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 GENECARDS:MAPK13 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13 mitogen-activated protein kinase 14 CSBP1 CSBP2 CSPB1 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 GENECARDS:MAPK14 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14 Mxi2 P38 "P38 MAP kinase" PRKM14 PRKM15 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="p38*"/> <bbox w="62.0" h="25.0" x="2889.2856" y="3083.8572"/> <glyph class="state variable" id="_c89e8b6a-2a5a-4f68-bf0f-5fc449db1463"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2884.2856" y="3095.989"/> </glyph> <glyph class="state variable" id="_58cb1285-fed1-40c7-9151-5392fb7ea6a8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2884.2856" y="3086.7832"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1027_mpk1_mpk1_csa109" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:SMAD3:SMAD4 Identifiers_end</body> </html> </notes> <label text="SMAD3:SMAD4"/> <bbox w="100.0" h="80.0" x="3730.0" y="2950.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s920_mpk1_mpk1_sa673"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: SMAD family member 3 "MAD mothers against decapentaplegic homolog 3 (Drosophila)" MADH3 "SMAD mothers against DPP homolog 3 (Drosophila)" HUGO:SMAD3 HGNC:6769 ENTREZ:4088 UNIPROT:P84022 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD3"/> <bbox w="50.0" h="25.0" x="3755.0" y="2957.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s915_mpk1_mpk1_sa676"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: SMAD family member 4 "MAD mothers against decapentaplegic homolog 4 (Drosophila)" MADH4 "SMAD mothers against DPP homolog 4 (Drosophila)" HUGO:SMAD4 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD4"/> <bbox w="50.0" h="25.0" x="3755.0" y="2981.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1028_mpk1_mpk1_csa108" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:SMAD2:SMAD4 Identifiers_end</body> </html> </notes> <label text="SMAD2:SMAD4"/> <bbox w="100.0" h="80.0" x="3610.0" y="2950.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s919_mpk1_mpk1_sa674"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: SMAD family member 2 "MAD mothers against decapentaplegic homolog 2 (Drosophila)" MADH2 "SMAD mothers against DPP homolog 2 (Drosophila)" HUGO:SMAD2 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end Identifiers_begin: SMAD family member 2 "MAD mothers against decapentaplegic homolog 2 (Drosophila)" MADH2 "SMAD mothers against DPP homolog 2 (Drosophila)" HUGO:SMAD2 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 GENECARDS:SMAD2 REACTOME:405890 KEGG:4087 ATLASONC:SMAD2ID370 WIKI:SMAD2 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD2"/> <bbox w="50.0" h="25.0" x="3635.0" y="2954.5"/> <glyph class="state variable" id="_eb766e1b-2121-4568-b415-63b5ff849596"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3680.0" y="2949.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s918_mpk1_mpk1_sa675"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: SMAD family member 4 "MAD mothers against decapentaplegic homolog 4 (Drosophila)" MADH4 "SMAD mothers against DPP homolog 4 (Drosophila)" HUGO:SMAD4 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD4"/> <bbox w="50.0" h="25.0" x="3635.0" y="2979.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1029_mpk1_mpk1_csa65" compartmentRef="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GPCR*:GRK* Identifiers_end</body> </html> </notes> <label text="GPCR*:GRK*"/> <bbox w="84.0" h="82.0" x="2114.0" y="2103.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s548_mpk1_mpk1_sa318"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2131.8333" y="2135.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s815_mpk1_mpk1_sa577"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="50.0" h="25.0" x="2132.818" y="2111.9092"/> <glyph class="state variable" id="_88c15f53-0bbb-4995-b874-7f7f711cd38a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2127.818" y="2119.4092"/> </glyph> <glyph class="unit of information" id="_5a5154dc-2e87-4a56-a0dc-e07a38b317dd"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2135.318" y="2106.9092"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1030_mpk1_mpk1_csa27" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="KSR1:MEK*"/> <bbox w="112.0" h="108.0" x="1687.0" y="1838.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s237_mpk1_mpk1_sa148"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="41.0" h="77.0" x="1697.0" y="1849.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s238_mpk1_mpk1_sa149"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1740.5" y="1874.5"/> <glyph class="state variable" id="_6e012b78-acf2-47c0-8870-9d567a1b5949"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1735.5" y="1886.1664"/> </glyph> <glyph class="state variable" id="_d5f6a6f3-8637-4bee-b614-7a9e1e9fbd51"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1735.5" y="1877.6261"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1031_mpk1_mpk1_csa26" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:KSR1-CTER*:MEK* Identifiers_end</body> </html> </notes> <label text="KSR1-CTER*:MEK*"/> <bbox w="134.0" h="85.0" x="2016.0" y="1871.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s213_mpk1_mpk1_sa131"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is cleaved by CASPASE3 in two regions: the C-ter region which mediates MEK binding and the N-ter region which contains the ERK binding site and the C1 domain required for plasma membrane localisation PMID:17613518 References_end</body> </html> </notes> <label text="KSR1-CTER*"/> <bbox w="119.0" h="26.0" x="2023.0" y="1880.0"/> <glyph class="unit of information" id="_98ea1947-d558-4009-a7a7-73ede59633bb"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="2057.5" y="1875.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s214_mpk1_mpk1_sa132"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="2055.5" y="1906.5"/> <glyph class="state variable" id="_c0135b82-8987-499a-a288-706963ae5b44"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2050.5" y="1918.833"/> </glyph> <glyph class="state variable" id="_aed36447-d6ad-42ca-a9b7-12a5d6685ea6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2050.5" y="1909.951"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1032_mpk1_mpk1_csa10" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IMP*:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="IMP*:KSR1:MEK*"/> <bbox w="163.0" h="109.0" x="2246.5" y="1896.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s80_mpk1_mpk1_sa60"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="49.0" h="76.0" x="2304.5" y="1906.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s81_mpk1_mpk1_sa61"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2349.5" y="1932.0"/> <glyph class="state variable" id="_e411be08-fede-4a6e-bc42-a1c22c8145dc"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2344.5" y="1943.6664"/> </glyph> <glyph class="state variable" id="_fe0d2cf4-6b7b-4034-b957-b5d253fe55c5"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2344.5" y="1935.1261"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s234_mpk1_mpk1_sa146"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: BRCA1 associated protein HUGO:BRAP HGNC:1099 ENTREZ:8315 UNIPROT:Q7Z569 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IMP (BRAP) is a RasGTP-interacting protein. It is constitutively bound to KSR1 blocking the enhancement of ERK activation (KSR1 is kept in an inactivated state) maybe recruiting KSR1 to microdomains inaccessible to activators of its function. This could be a mechanism to limit the engagement of ERK cascade in the absence of Ras activation. PMID:14724641 References_end</body> </html> </notes> <label text="IMP*"/> <bbox w="50.0" h="25.0" x="2254.5" y="1931.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1033_mpk1_mpk1_csa61" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="ERK*:KSR1:MEK*"/> <bbox w="136.0" h="110.0" x="1623.0" y="2034.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s519_mpk1_mpk1_sa298"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="50.0" h="25.0" x="1637.3334" y="2042.6667"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s520_mpk1_mpk1_sa299"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1683.3334" y="2069.6667"/> <glyph class="state variable" id="_16aaf359-a600-44c1-8097-343716ec1aec"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2081.333"/> </glyph> <glyph class="state variable" id="_78fa69b0-9958-43fa-81a9-338da27e9f69"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2072.7927"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s521_mpk1_mpk1_sa300"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="1683.3334" y="2094.6667"/> <glyph class="state variable" id="_d1c97124-7b19-47cd-b94b-b911096839bc"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2106.5234"/> </glyph> <glyph class="state variable" id="_681d90ac-9f22-4198-8588-8727991a7d4c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2097.2168"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1034_mpk1_mpk1_csa62" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="ERK*:KSR1:MEK*"/> <bbox w="134.0" h="112.0" x="1835.0" y="2058.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s526_mpk1_mpk1_sa303"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="50.0" h="25.0" x="1852.6666" y="2069.6667"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s527_mpk1_mpk1_sa304"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1896.6666" y="2093.6667"/> <glyph class="state variable" id="_a92fe4ce-d1ff-4891-a5d0-a510f3dbe38c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.1666" y="2105.333"/> </glyph> <glyph class="state variable" id="_5d449f91-4ed1-4335-8531-f89e125f39fb"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.1666" y="2096.7927"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="mpk1_mpk1_s530_mpk1_mpk1_sa307"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - ERK represents both ERK1 and ERK2 because it is not completely clear when the two isoforms behave differently. This also happens for the activation on late endosomes: it is known that only ERK1 is activated there, however when ERK1 reaches nucleus, it behaves like ERK2. - Once activated, ERK may either keep being in complex with its activators and scaffolds, or be released in the cytoplasm. In the latter case, it may either dimerise, being able to activate its cytoplasmic targets, or not, being able to translocate to the nucleus. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="1897.0834" y="2119.1667"/> <glyph class="unit of information" id="_72092276-8367-4983-b74d-f2d4d32c4098"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="1912.0834" y="2114.1667"/> </glyph> <glyph class="state variable" id="_02994043-9360-4421-8cdb-167e4aeee07c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.5834" y="2131.0234"/> </glyph> <glyph class="state variable" id="_2cb57c32-95a6-4414-a50c-0c794abc5d39"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.5834" y="2121.7168"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1035_mpk1_mpk1_csa95" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GADD45*:MAP3K4 Identifiers_end</body> </html> </notes> <label text="GADD45*:MAP3K4"/> <bbox w="127.0" h="84.0" x="3871.9963" y="2233.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s738_mpk1_mpk1_sa511"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: growth arrest and DNA-damage-inducible alpha DDIT1 HUGO:GADD45A HGNC:4095 ENTREZ:1647 UNIPROT:P24522 growth arrest and DNA-damage-inducible beta MYD118 HUGO:GADD45B HGNC:4096 ENTREZ:4616 UNIPROT:O75293 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Expression of GADD45 is the culmination of a signalling pathway that requires prior expression of the tumour suppressor protein P53 which trans-activates the gadd45 gene. P53 expression is in turn driven by the activity of the ATM gene product. GADD45alpha/beta are direct MEKK4 interactors. They are involved in genotoxin regulation of MEKK4 signalling to JNK and P38. PMID:11274345 References_end</body> </html> </notes> <label text="GADD45*"/> <bbox w="75.0" h="25.0" x="3904.4963" y="2239.6667"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s739_mpk1_mpk1_sa512"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase kinase 4 MEKK4 HUGO:MAP3K4 HGNC:6856 ENTREZ:4216 UNIPROT:Q9Y6R4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MEKK4 is a MAP3K and can activate both JNK and P38 pathways. It may be an effector for stress pathways activated by genotoxins. PMID:11274345 References_end</body> </html> </notes> <label text="MAP3K4"/> <bbox w="73.0" h="26.0" x="3901.4963" y="2263.6667"/> <glyph class="state variable" id="_743f2a0c-1013-4c8a-9013-09cca78f56a5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="3893.9963" y="2271.6667"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1036_mpk1_mpk1_csa82" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TAB*:TAK1*:TGFBR1:TGFBR2 Identifiers_end</body> </html> </notes> <label text="TAB*:TAK1*:TGFBR1:TGFBR2"/> <bbox w="199.0" h="85.0" x="3626.9963" y="2238.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s58_mpk1_mpk1_sa459"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TGF-beta activated kinase 1/MAP3K7 binding protein 1 MAP3K7IP1 "mitogen-activated protein kinase kinase kinase 7 interacting protein 1" HUGO:TAB1 HGNC:18157 ENTREZ:10454 UNIPROT:Q15750 TGF-beta activated kinase 1/MAP3K7 binding protein 2 MAP3K7IP2 "mitogen-activated protein kinase kinase kinase 7 interacting protein 2" HUGO:TAB2 HGNC:17075 ENTREZ:23118 UNIPROT:Q9NYJ8 TGF-beta activated kinase 1/MAP3K7 binding protein 3 MAP3K7IP3 "mitogen-activated protein kinase kinase kinase 7 interacting protein 3" HUGO:TAB3 HGNC:30681 ENTREZ:257397 UNIPROT:Q8N5C8 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TAK1 is the only MAP3K that requires the adapter proteins TAB123 for its activation. PMID:20060931 References_end</body> </html> </notes> <label text="TAB*"/> <bbox w="50.0" h="25.0" x="3668.163" y="2271.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s59_mpk1_mpk1_sa460"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 TAK1 HUGO:MAP3K7 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways. Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6. PMID:18855897 PMID:11274345 References_end Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 TAK1 HUGO:MAP3K7 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 GENECARDS:MAP3K7 REACTOME:168070 KEGG:6885 ATLASONC:MAP3K7ID454ch6q15 WIKI:MAP3K7 MEKK7 MEKK7 TAK1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways. Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6. PMID:18855897 PMID:11274345 References_end</body> </html> Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 TAK1 HUGO:MAP3K7 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 GENECARDS:MAP3K7 REACTOME:168070 KEGG:6885 ATLASONC:MAP3K7ID454ch6q15 WIKI:MAP3K7 MEKK7 MEKK7 TAK1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways. Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6. PMID:18855897 PMID:11274345 References_end</body> </html> </notes> <label text="TAK1*"/> <bbox w="73.0" h="26.0" x="3717.163" y="2270.0"/> <glyph class="state variable" id="_0b02f140-051a-4ee9-9b62-9930ff2a76c8"> <state value="" variable="T187"/> <bbox w="30.0" h="10.0" x="3702.6125" y="2265.0"/> </glyph> <glyph class="state variable" id="_c0e6c0ae-75da-4993-819b-183679a3283b"> <state value="" variable="S192"/> <bbox w="30.0" h="10.0" x="3774.5989" y="2291.0"/> </glyph> <glyph class="state variable" id="_7626ee73-bc3b-4f1f-9444-05e8032fbffe"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="3709.663" y="2278.0"/> </glyph> <glyph class="state variable" id="_5338c10e-5a46-4ae7-aca1-bd004c978dd2"> <state value="" variable="T184"/> <bbox w="30.0" h="10.0" x="3702.6125" y="2265.0"/> </glyph> <glyph class="state variable" id="_810bdb33-decc-47e0-bc4d-00f2afd01d87"> <state value="" variable="T178"/> <bbox w="30.0" h="10.0" x="3702.163" y="2290.8196"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s813_mpk1_mpk1

</head> <body>Wang et al. (2002) have shown that EGFR signalling from endosomes leads to cell survival. 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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Endosome"> <bbox w="45.0" h="10.0" x="2557.5" y="2515.5"/> </label> <bbox w="97.0" h="207.0" x="14844.0" y="2399.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c4_wca1_wca1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>21183076</body> </html> </notes> <label text="Vaceolae"> <bbox w="45.0" h="10.0" x="1278.5" y="351.5"/> </label> <bbox w="1515.0" h="369.0" x="13545.0" y="84.0"/> </glyph> <glyph class="compartment" id="wca1_wca1_c6_wca1_wca1_ca10" compartmentRef="wca1_wca1_c1_wca1_wca1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> 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x="432.5" y="2442.5"/> </label> <bbox w="2470.0" h="2392.0" x="17952.0" y="156.0"/> </glyph> <glyph class="compartment" id="shh1_shh2_c1_shh1_shh2_ca1"> <label text="Cytosol"> <bbox w="40.0" h="10.0" x="1230.5" y="2667.5"/> </label> <bbox w="2489.0" h="2197.0" x="17951.0" y="2655.0"/> </glyph> <glyph class="compartment" id="shh1_shh2_c1_shh1_shh3_ca1"> <label text="Cytosol"> <bbox w="40.0" h="10.0" x="1257.5" y="4979.5"/> </label> <bbox w="2400.0" h="857.0" x="17981.0" y="4959.0"/> </glyph> <glyph class="macromolecule" id="gf1_s14_gf1_sa30" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PDGFA HUGO:PDGFB HUGO:PDGFC HUGO:PDGFD MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23123598 PDGF stimulation of CAFs induces production of the prototypical pro-angiogenic inducer fibroblast growth factor (FGF)-2 in both cervical carcinomas and melanoma [11] and [85]. Interestingly, CAFs activated by PDGF-CC in melanomas also secrete the extracellular matrix protein osteopontin, the action of which is known to synergistically stimulate angiogenesis together with FGF-2 and promote autocrine VEGF-A signaling in endothelial cells PMID:15207817; PMID:19118022 PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Tumor fibroblasts a recruted by PDGF PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR?? and ??, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells</body> </html> </notes> <label text="PDGF*"/> <bbox w="80.0" h="40.0" x="273.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4526_gf1_sa32" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGF1 HUGO:FGF2 HUGO:FGF3 HUGO:FGF4 HUGO:FGF5 HUGO:FGF6 HUGO:FGF7 HUGO:FGF8 HUGO:FGF9 HUGO:FGF10 HUGO:FGF11 HUGO:FGF12 HUGO:FGF13 HUGO:FGF14 HUGO:FGF16 HUGO:FGF17 HUGO:FGF18 HUGO:FGF19 HUGO:FGF20 HUGO:FGF21 HUGO:FGF22 HUGO:FGF23 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Deregulation of FGF signaling pathways have been implicated in many types of human and animal cancers.</body> </html> </notes> <label text="FGF*"/> <bbox w="80.0" h="40.0" x="612.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s423_gf1_sa35" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PGDFRA HUGO:PGDFRB MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR alpha and beta, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGFRA binds to all PDGF isoforms except PDGF-DD, while PDGFRB is activated by PDGF-BB and -DD. PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells . The large protein complex recruited by phosphorylated PDGF receptors is seen as a dynamic signalosome that controls cell fate.</body> </html> </notes> <label text="PDGFR*"/> <bbox w="80.0" h="50.0" x="402.5" y="322.5"/> <glyph class="unit of information" id="_cfb9f562-7303-40b5-9d22-98a3b1098d92"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="420.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4554_gf1_sa37" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:FRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Downstream of the signaling tyrosine kinase FGFRs, intracellular signaling cascades are also tightly regulated by specialized adaptor proteins such as FGFR substrate 2?? (FRS2??) and regulators of the RAS???MAPK and PI3K???AKT pathways such as Sprouty (SPRY) proteins Identifiers_begin: fibroblast growth factor receptor substrate 2 HUGO:FRS2 HGNC:16971 ENTREZ:10818 UNIPROT:Q8WU20 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="FRS2"/> <bbox w="80.0" h="40.0" x="743.5" y="777.5"/> <glyph class="state variable" id="_88f497f6-47b9-45d5-a401-96eed3e320e7"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="736.0" y="792.5"/> </glyph> <glyph class="state variable" id="_e6cf9f56-a9ee-4c5a-a77e-20d0e7b8a961"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="738.5" y="792.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4547_gf1_sa38" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:FRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Downstream of the signaling tyrosine kinase FGFRs, intracellular signaling cascades are also tightly regulated by specialized adaptor proteins such as FGFR substrate 2?? (FRS2??) and regulators of the RAS???MAPK and PI3K???AKT pathways such as Sprouty (SPRY) proteins Identifiers_begin: fibroblast growth factor receptor substrate 2 HUGO:FRS2 HGNC:16971 ENTREZ:10818 UNIPROT:Q8WU20 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="FRS2"/> <bbox w="80.0" h="40.0" x="742.5" y="667.5"/> <glyph class="state variable" id="_6586a8f8-b596-4528-97c5-f6b65d3b40f2"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="737.5" y="682.5"/> </glyph> <glyph class="state variable" id="_a313650d-c386-43d5-a1ec-9de79ba78ea5"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="737.5" y="682.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4735_gf1_sa42" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGFR1 HUGO:FGFR2 HUGO:FGFR3 HUGO:FGFR4 HUGO:FGFRL1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25467007 FGFRs _rew PMID:25772309 Binding of canonical FGFs to FGFR with HS (or HSPG) as a cofactor induces the formation of ternary FGF???FGFR???HS complex, which activates the FGFR intracellular tyrosine kinase domain by phosphorylation of specific tyrosine residues. The activated receptor is coupled to intracellular signaling pathways including the RAS???MAPK, PI3K???AKT, PLC??, and STAT pathways.</body> </html> </notes> <label text="FGFR*"/> <bbox w="80.0" h="50.0" x="722.5" y="322.5"/> <glyph class="unit of information" id="_5aaf00f0-642b-4d22-a4a7-f19e613fdf9c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="740.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4506_gf1_sa44" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:AREG MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="AREG"/> <bbox w="80.0" h="40.0" x="1192.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s416_gf1_sa45" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:ERBB2 HUGO:ERBB3 HUGO:ERBB4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40).</body> </html> </notes> <label text="ERBB*"/> <bbox w="80.0" h="50.0" x="1522.5" y="322.5"/> <glyph class="unit of information" id="_9ff62a8a-d756-4279-a344-4a8fffd382c7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1540.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s102_gf1_sa46" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:EGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="EGF"/> <bbox w="80.0" h="40.0" x="1482.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s415_gf1_sa48" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:EGFR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40). PMID:28513565 Epidermal growth factor receptor (EGFR) signaling pathways leading to G1/S cell cycle progression activated by EGF activation. Depicted are the RAS-RAF-MEK-ERK MAPK and PI3K-AKT-mTOR pathways. Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)", ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="EGFR"/> <bbox w="80.0" h="50.0" x="1462.5" y="432.5"/> <glyph class="unit of information" id="_d604d9b7-31e5-42b4-af5d-33543525e60f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1480.0" y="427.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4593_gf1_sa52" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2R MODULE:GROWTH_FACTORS_SIGNALING_PATHWAYS PMID:27548915 One function of IGF2R is to bind to the ligand IGF2, leading to IGF2 degradation and consequently an inhibition of the growth stimulation that results from the interaction between IGF2 and IGF1R48, 49. IGF2 is upregulated in CAFs50, suggesting that IGF2R is inhibited. Therefore, reduction in IGF2R following treatment with miR-211 or melanosomes may increase IGF2 levels, promoting its binding to IGF1R, and thus leading to hyperactivation of this pathway and increased proliferation.</body> </html> </notes> <label text="IGF2R"/> <bbox w="80.0" h="50.0" x="2172.5" y="322.5"/> <glyph class="unit of information" id="_47f9061b-afdf-4891-b13a-26f064ef6dce"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2190.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4508_gf1_sa53" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:24668028 IGF2 expressed by CAFs promotes tumor growth PMID:11237532 In breast cancers, both IGF-I and IGF-II are expressed in the stromal ???broblasts and expression of IGF-II in particular correlates with tumor progression</body> </html> </notes> <label text="IGF2"/> <bbox w="80.0" h="40.0" x="1922.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4564_gf1_sa55" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IRS1 HUGO:IRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:8621421 Grb2- and Shc-SH2 domain binding to phosphopeptides from rat IRS-1 PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IRS*"/> <bbox w="80.0" h="40.0" x="1952.5" y="757.5"/> <glyph class="state variable" id="_d9a192ac-b880-42a8-8b7d-165bcab98c1c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1945.0" y="772.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4563_gf1_sa56" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IRS1 HUGO:IRS2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:8621421 Grb2- and Shc-SH2 domain binding to phosphopeptides from rat IRS-1 PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IRS*"/> <bbox w="80.0" h="40.0" x="1952.5" y="657.5"/> <glyph class="state variable" id="_3232804e-00af-4cfa-9661-9507592ad641"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1947.5" y="672.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4565_gf1_sa57" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IGF1R"/> <bbox w="80.0" h="50.0" x="1852.5" y="522.5"/> <glyph class="state variable" id="_c60490bb-1655-4f3f-9486-6e7c2924c8c2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1845.0" y="542.5"/> </glyph> <glyph class="unit of information" id="_46b1502a-4b09-41a4-ba87-b23b663576ed"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1870.0" y="517.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4515_gf1_sa58" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:12175651; PMID:10086337 Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.</body> </html> </notes> <label text="IGF1R"/> <bbox w="80.0" h="50.0" x="1852.5" y="322.5"/> <glyph class="state variable" id="_4138c239-7657-4c3c-93cd-418946c4e78b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1847.5" y="342.5"/> </glyph> <glyph class="unit of information" id="_8e962ec9-9569-4527-af01-6c617157efd7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1870.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4519_gf1_sa59" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 20388853 Upon binding by either IGF-1 or IGF-2, the IGF-1R undergoes receptor cross-linking and autophosphorylation, leading to the creation of multiple docking sites for the adaptor proteins IRS-1, IRS-2, and Shc.</body> </html> </notes> <label text="IGF1"/> <bbox w="80.0" h="40.0" x="2072.5" y="127.5"/> </glyph> <glyph class="source and sink" id="gf1_s4597_gf1_sa63" compartmentRef="gf1_c1_gf1_ca1"> <label text="csa102_degraded"/> <bbox w="30.0" h="30.0" x="2247.5" y="662.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4529_gf1_sa65" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MET MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121; PMID:20303741 Upon HGF binding, Met autophosphorylation occurs on tyrosine residues Y1234 and Y1235 (numbered according to GenBank J02958) within the activation loop of the TK domain, inducing kinase activity, while phosphorylation on Y1349 and Y1356 near the carboxyl terminus forms a docking site for intracellular adapters that transmit signals downstream.6, 8 An intact docking site is required for transformation and metastasis.8 Critical signalling mediators in this pathway include Grb2, Gab1, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma (PLC??), Shc, Src, Shp2, Ship1 and STAT3.6, 8</body> </html> </notes> <label text="MET"/> <bbox w="80.0" h="50.0" x="2372.5" y="322.5"/> <glyph class="state variable" id="_227dae45-6856-4b81-8d39-67a0069a88f5"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2367.5" y="342.5"/> </glyph> <glyph class="unit of information" id="_d0961bd5-23c9-4c2b-9481-d78c3a272695"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2390.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4468_gf1_sa66" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:HGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121 Hepatocyte growth factor (HGF) induces cancer cell migration and invasion.</body> </html> </notes> <label text="HGF"/> <bbox w="80.0" h="40.0" x="2462.5" y="127.5"/> </glyph> <glyph class="complex" id="gf1_s417_gf1_csa8" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>PMID:7682895; PMID:17397400 PDGF -receptor directly binds and activates PLC-gamma 1, RasGAP, P13K, and a 64 kd protein. PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts downstream of PDGF signaling</body> </html> </notes> <label text="gf1_s417"/> <bbox w="100.0" h="130.0" x="212.5" y="492.5"/> <glyph class="macromolecule" id="gf1_s413_gf1_sa106"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PGDFRA HUGO:PGDFRB MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR alpha and beta, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGFRA binds to all PDGF isoforms except PDGF-DD, while PDGFRB is activated by PDGF-BB and -DD. PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells . The large protein complex recruited by phosphorylated PDGF receptors is seen as a dynamic signalosome that controls cell fate.</body> </html> </notes> <label text="PDGFR*"/> <bbox w="80.0" h="50.0" x="222.5" y="552.5"/> <glyph class="unit of information" id="_c4144bc4-a27b-4307-8729-50e48cab343e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="240.0" y="547.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s424_gf1_sa107"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:PDGFA HUGO:PDGFB HUGO:PDGFC HUGO:PDGFD MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23123598 PDGF stimulation of CAFs induces production of the prototypical pro-angiogenic inducer fibroblast growth factor (FGF)-2 in both cervical carcinomas and melanoma [11] and [85]. Interestingly, CAFs activated by PDGF-CC in melanomas also secrete the extracellular matrix protein osteopontin, the action of which is known to synergistically stimulate angiogenesis together with FGF-2 and promote autocrine VEGF-A signaling in endothelial cells PMID:15207817; PMID:19118022 PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Tumor fibroblasts a recruted by PDGF PMID: 24703957 PDGFs are encoded by four different genes: PDGF-A, -B, -C and -D, which are related to VEGF and belong to the ???cystine knots??? protein superfamily The two PDGF receptors, namely PDGFR?? and ??, are receptor tyrosine kinases (RTK) belonging to the so-called type III family, which also includes c-KIT, c-FMS and FLT3 (the receptors of stem cell factor, CSF1 and FLT3-ligand, respectively). They are more distantly related to the receptors of VEGF and fibroblast growth factors (FGF). PDGF ligands and receptors are proto-oncogenes that can be activated by various types of genetic alterations in cancer cells</body> </html> </notes> <label text="PDGF*"/> <bbox w="80.0" h="40.0" x="222.5" y="507.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s419_gf1_csa10" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s419"/> <bbox w="100.0" h="142.5" x="1172.5" y="506.25"/> <glyph class="macromolecule" id="gf1_s421_gf1_sa110"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:EGFR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40). PMID:28513565 Epidermal growth factor receptor (EGFR) signaling pathways leading to G1/S cell cycle progression activated by EGF activation. Depicted are the RAS-RAF-MEK-ERK MAPK and PI3K-AKT-mTOR pathways. Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)", ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="EGFR"/> <bbox w="80.0" h="50.0" x="1182.5" y="523.75"/> <glyph class="unit of information" id="_13486e9e-383c-46e4-90bc-348f391b34f6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1200.0" y="518.75"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s422_gf1_sa111"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:ERBB2 HUGO:ERBB3 HUGO:ERBB4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953 All EGF family members bind to a group of four receptor tyrosine kinases, namely ErbB-1/EGFR through -4 (also called HER1???4). Like other tyrosine kinases, each ErbB molecule comprises an extracellular domain to allow ligand binding, a single transmembrane part, and an intracellular protein tyrosine kinase domain. It is important noting that not all ErbB receptors act autonomously: ErbB-2 (also called HER2 and Neu) binds no known EGF-like ligand (56), and ErbB-3 shows no tyrosine kinase activity (40).</body> </html> </notes> <label text="ERBB*"/> <bbox w="80.0" h="50.0" x="1182.5" y="573.75"/> <glyph class="unit of information" id="_6db49f90-8343-4e05-b0b5-bf1ecf474d7f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1200.0" y="568.75"/> </glyph> </glyph> </glyph> <glyph class="complex" id="gf1_s4594_gf1_csa13" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s4594"/> <bbox w="100.0" h="120.0" x="2102.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s4807_gf1_sa116"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2R MODULE:GROWTH_FACTORS_SIGNALING_PATHWAYS PMID:27548915 One function of IGF2R is to bind to the ligand IGF2, leading to IGF2 degradation and consequently an inhibition of the growth stimulation that results from the interaction between IGF2 and IGF1R48, 49. IGF2 is upregulated in CAFs50, suggesting that IGF2R is inhibited. Therefore, reduction in IGF2R following treatment with miR-211 or melanosomes may increase IGF2 levels, promoting its binding to IGF1R, and thus leading to hyperactivation of this pathway and increased proliferation.</body> </html> </notes> <label text="IGF2R"/> <bbox w="80.0" h="50.0" x="2112.5" y="572.5"/> <glyph class="unit of information" id="_0570584b-b192-4067-8e1a-c08dddd12cc1"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2130.0" y="567.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s4596_gf1_sa117"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:IGF2 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:24668028 IGF2 expressed by CAFs promotes tumor growth PMID:11237532 In breast cancers, both IGF-I and IGF-II are expressed in the stromal ???broblasts and expression of IGF-II in particular correlates with tumor progression</body> </html> </notes> <label text="IGF2"/> <bbox w="80.0" h="40.0" x="2112.5" y="527.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s4530_gf1_csa15" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s4530"/> <bbox w="100.0" h="120.0" x="2452.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s4825_gf1_sa120"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:HGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121 Hepatocyte growth factor (HGF) induces cancer cell migration and invasion.</body> </html> </notes> <label text="HGF"/> <bbox w="80.0" h="40.0" x="2462.5" y="527.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4826_gf1_sa121"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MET MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:28475121; PMID:20303741 Upon HGF binding, Met autophosphorylation occurs on tyrosine residues Y1234 and Y1235 (numbered according to GenBank J02958) within the activation loop of the TK domain, inducing kinase activity, while phosphorylation on Y1349 and Y1356 near the carboxyl terminus forms a docking site for intracellular adapters that transmit signals downstream.6, 8 An intact docking site is required for transformation and metastasis.8 Critical signalling mediators in this pathway include Grb2, Gab1, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma (PLC??), Shc, Src, Shp2, Ship1 and STAT3.6, 8</body> </html> </notes> <label text="MET"/> <bbox w="80.0" h="50.0" x="2462.5" y="572.5"/> <glyph class="state variable" id="_3021eab2-66b1-438d-9ea7-91b15b2d2dd2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2455.0" y="592.5"/> </glyph> <glyph class="unit of information" id="_555cd1e1-402e-4b39-8601-4ccbf260dcca"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2480.0" y="567.5"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s1_gf1_sa130" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:TGFA MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="TGFA"/> <bbox w="80.0" h="40.0" x="1102.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s2_gf1_sa131" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:NRG1 HUGO:NRG2 HUGO:NRG3 HUGO:NRG4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="NRG*"/> <bbox w="80.0" h="40.0" x="1282.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s3_gf1_sa132" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:BTC MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="BTC"/> <bbox w="80.0" h="40.0" x="1002.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s4_gf1_sa133" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:EREG MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="EREG"/> <bbox w="80.0" h="40.0" x="1612.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s5_gf1_sa134" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:HBEGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="HBEGF"/> <bbox w="80.0" h="40.0" x="902.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s6_gf1_sa135" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:EPGN MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:20430953</body> </html> </notes> <label text="EPGN"/> <bbox w="80.0" h="40.0" x="1382.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s5191_gf1_sa136" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3262.5" y="127.5"/> </glyph> <glyph class="macromolecule" id="gf1_s3913_gf1_sa138" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS HUGO:FLT1 PMID: 28560064 Expression of Flt1 promotes glioblastoma cells migration, invasion</body> </html> </notes> <label text="FLT1"/> <bbox w="80.0" h="50.0" x="3602.5" y="322.5"/> <glyph class="unit of information" id="_a0875011-b423-430c-8a85-56bc26a7f962"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3620.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s7_gf1_sa143" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FLT4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16530705 The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells</body> </html> </notes> <label text="FLT4"/> <bbox w="80.0" h="50.0" x="2982.5" y="322.5"/> <glyph class="unit of information" id="_d63a3aa2-2849-4bef-8759-d815fed4e5b8"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3000.0" y="317.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s8_gf1_sa144" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:MST1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. Identifiers_begin: macrophage stimulating 1 (hepatocyte growth factor-like) D3F15S2 DNF15S2 HGFL HUGO:MST1 HGNC:7380 ENTREZ:4485 UNIPROT:P26927 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="MST1"/> <bbox w="80.0" h="40.0" x="2672.5" y="127.5"/> <glyph class="state variable" id="_4f7dfb7d-f969-4df8-976f-b27c05239a03"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2667.5" y="142.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s9_gf1_sa145" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MST1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. RON activation results in the autophosphorylation of Tyr1238 and Tyr1239 at the A-loop (Phe1227???Pro1250) in the kinase domain93,95,98. Phosphorylation of these regulatory residues then activates the kinase activity, leading to further phosphorylation of Tyr1353 and Tyr1360 in the C-terminal docking site. The docking site interacts with downstream signalling proteins, triggering multiple intracellular pathways MSP???RON signalling activates two classical signalling pathways, RAS???ERK and PI3K???AKT, both of which interact with various other pathways to create a complex signalling network.</body> </html> </notes> <label text="MST1R"/> <bbox w="80.0" h="50.0" x="2802.5" y="322.5"/> <glyph class="state variable" id="_8d5a1203-c48d-45f6-98eb-d1abbd577a22"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2797.5" y="342.5"/> </glyph> <glyph class="unit of information" id="_ef52596d-d6bf-48f0-9f8c-b3f37d3e2a4e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2820.0" y="317.5"/> </glyph> </glyph> <glyph class="phenotype" id="gf1_s5192_gf1_sa146" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:28513565 EGFR pathways PMID:20388853 IGFR1 pathways PMID:23792360 MST1 pathways PMID:20303741 HGF</body> </html> </notes> <label text="MAPK_PATHWAYS"/> <bbox w="432.5" h="43.75" x="2506.25" y="1085.625"/> </glyph> <glyph class="phenotype" id="gf1_s5193_gf1_sa147" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:28513565 EGFR pathways PMID:28475121 HGF/MET PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="PLCG_PATHWAYS"/> <bbox w="435.0" h="47.5" x="1195.0" y="1053.75"/> </glyph> <glyph class="phenotype" id="gf1_s5194_gf1_sa148" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:28513565 EGFR pathways PMID: 20388853 IGF1R PMID:23792360 MST1 pathways PMID:28475121 HGF/MET PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="PI3K_PATHWAY"/> <bbox w="415.0" h="42.5" x="1815.0" y="1146.25"/> </glyph> <glyph class="phenotype" id="gf1_s5196_gf1_sa150" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID: 24703957 PDGFs pathways PMID:25772309 FGFs pathways PMID:24675568 EGFR/JAK/STAT STAT3 is a critical mediator of the oncogenic effects of EGFR mutations PMID:20303741 HGF</body> </html> </notes> <label text="JAK/STAT_PATHWAY"/> <bbox w="345.0" h="42.5" x="710.0" y="1146.25"/> </glyph> <glyph class="macromolecule" id="gf1_s5197_gf1_sa151" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KL MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 The Fgf15/19 subfamily members encode endocrine FGFs, which bind to and activate FGFRs with the Klotho family protein as a cofactor.</body> </html> </notes> <label text="KL"/> <bbox w="80.0" h="40.0" x="902.5" y="547.5"/> </glyph> <glyph class="macromolecule" id="gf1_s5198_gf1_sa152" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KLB MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 The Fgf15/19 subfamily members encode endocrine FGFs, which bind to and activate FGFRs with the Klotho family protein as a cofactor.</body> </html> </notes> <label text="KLB"/> <bbox w="80.0" h="40.0" x="902.5" y="467.5"/> </glyph> <glyph class="simple chemical" id="gf1_s5199_gf1_sa153" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Canonical FGFs are tightly bound to heparin/heparan sulfate (HS) proteoglycans (HSPGs), which function to limit diffusion through the extracellular matrix (ECM) and serve as cofactors that regulate specificity and affinity for signaling FGFRs.</body> </html> </notes> <label text="HSPGs*"/> <bbox w="70.0" h="25.0" x="907.5" y="395.0"/> </glyph> <glyph class="complex" id="gf1_s5200_gf1_csa22" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s5200"/> <bbox w="100.0" h="120.0" x="622.5" y="507.5"/> <glyph class="macromolecule" id="gf1_s5201_gf1_sa41"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGFR1 HUGO:FGFR2 HUGO:FGFR3 HUGO:FGFR4 HUGO:FGFRL1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25467007 FGFRs _rew PMID:25772309 Binding of canonical FGFs to FGFR with HS (or HSPG) as a cofactor induces the formation of ternary FGF???FGFR???HS complex, which activates the FGFR intracellular tyrosine kinase domain by phosphorylation of specific tyrosine residues. The activated receptor is coupled to intracellular signaling pathways including the RAS???MAPK, PI3K???AKT, PLC??, and STAT pathways.</body> </html> </notes> <label text="FGFR*"/> <bbox w="80.0" h="50.0" x="632.5" y="562.5"/> <glyph class="unit of information" id="_7d803cf0-0f78-4048-b5bf-920c3cd3713c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="650.0" y="557.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s5202_gf1_sa154"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FGF1 HUGO:FGF2 HUGO:FGF3 HUGO:FGF4 HUGO:FGF5 HUGO:FGF6 HUGO:FGF7 HUGO:FGF8 HUGO:FGF9 HUGO:FGF10 HUGO:FGF11 HUGO:FGF12 HUGO:FGF13 HUGO:FGF14 HUGO:FGF16 HUGO:FGF17 HUGO:FGF18 HUGO:FGF19 HUGO:FGF20 HUGO:FGF21 HUGO:FGF22 HUGO:FGF23 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:25772309 Deregulation of FGF signaling pathways have been implicated in many types of human and animal cancers.</body> </html> </notes> <label text="FGF*"/> <bbox w="80.0" h="40.0" x="632.5" y="517.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s5203_gf1_csa23" compartmentRef="gf1_c1_gf1_ca1"> <label text="gf1_s5203"/> <bbox w="100.0" h="120.0" x="2662.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s5204_gf1_sa156"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>HUGO:MST1 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. Identifiers_begin: macrophage stimulating 1 (hepatocyte growth factor-like) D3F15S2 DNF15S2 HGFL HUGO:MST1 HGNC:7380 ENTREZ:4485 UNIPROT:P26927 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end</body> </html> </notes> <label text="MST1"/> <bbox w="80.0" h="40.0" x="2672.5" y="527.5"/> <glyph class="state variable" id="_d931b33d-72e8-42dd-a4dd-4130e2586bf9"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2667.5" y="542.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s5205_gf1_sa157"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:MST1R MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:23792360 Both in vitro and in vivo evidence has revealed that MSP???RON signalling is important for the invasive growth of different types of cancers. RON activation results in the autophosphorylation of Tyr1238 and Tyr1239 at the A-loop (Phe1227???Pro1250) in the kinase domain93,95,98. Phosphorylation of these regulatory residues then activates the kinase activity, leading to further phosphorylation of Tyr1353 and Tyr1360 in the C-terminal docking site. 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xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:FLT4 MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16530705 The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells</body> </html> </notes> <label text="FLT4"/> <bbox w="80.0" h="50.0" x="3042.5" y="562.5"/> <glyph class="unit of information" id="_08655090-509c-4c49-a4f1-a36a8c17c0d6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3060.0" y="557.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s5208_gf1_sa159"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3042.5" y="527.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s3866_gf1_sa137" compartmentRef="gf1_c1_gf1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KDR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:17883421 Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer</body> </html> </notes> <label text="KDR"/> <bbox w="80.0" h="50.0" x="3252.5" y="322.5"/> <glyph class="unit of information" id="_02ed7b2e-e650-4793-b8a1-641d5b292e86"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3270.0" y="317.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s5209_gf1_csa20" compartmentRef="gf1_c1_gf1_ca1"> <label text="KDR:VEGF*"/> <bbox w="100.0" h="120.0" x="3292.5" y="517.5"/> <glyph class="macromolecule" id="gf1_s3910_gf1_sa139"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:KDR MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:17883421 Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer</body> </html> </notes> <label text="KDR"/> <bbox w="80.0" h="50.0" x="3302.5" y="572.5"/> <glyph class="unit of information" id="_9dafa460-33d8-45cf-b0af-045bd3c89b6e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3320.0" y="567.5"/> </glyph> </glyph> <glyph class="macromolecule" id="gf1_s3911_gf1_sa140"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3302.5" y="527.5"/> </glyph> </glyph> <glyph class="complex" id="gf1_s5210_gf1_csa21" compartmentRef="gf1_c1_gf1_ca1"> <label text="FLT1:VEGF*"/> <bbox w="100.0" h="130.0" x="3542.5" y="512.5"/> <glyph class="macromolecule" id="gf1_s4495_gf1_sa142"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>HUGO:VEGFA HUGO:VEGFB HUGO:VEGFC HUGO:VEGFD HUGO:PGF MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS PMID:16951216 Vascular Endothelial Growth Factor Signaling Pathways</body> </html> </notes> <label text="VEGF*"/> <bbox w="80.0" h="40.0" x="3552.5" y="517.5"/> </glyph> <glyph class="macromolecule" id="gf1_s3915_gf1_sa141"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>MODULE:GROWTH_FACTORS_LIGANDS_RECEPTORS HUGO:FLT1 PMID: 28560064 Expression of Flt1 promotes glioblastoma cells migration, invasion</body> </html> </notes> <label text="FLT1"/> <bbox w="80.0" h="50.0" x="3552.5" y="572.5"/> <glyph class="unit of information" id="_7f54f128-764c-40c3-b64a-d49391973b84"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3570.0" y="567.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s23_mpk1_mpk1_csa75" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TNFRSF1B:TRAF2 Identifiers_end</body> </html> </notes> <label text="TNFRSF1B:TRAF2"/> <bbox w="132.0" h="80.0" x="2725.9963" y="1509.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s727_mpk1_mpk1_sa439"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2765.4963" y="1540.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s24_mpk1_mpk1_sa440"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1B TNFR2 HUGO:TNFRSF1B HGNC:11917 ENTREZ:7133 UNIPROT:P20333 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins (TRAF2). PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1B"/> <bbox w="70.0" h="25.0" x="2757.4963" y="1516.0"/> <glyph class="unit of information" id="_0022ef53-ef9f-4182-8d9e-bbb6c705158a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2769.9963" y="1511.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s14_mpk1_mpk1_csa74" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:RIPK1:TNFRSF1A:TRADD:TRAF2 Identifiers_end</body> </html> </notes> <label text="RIPK1:TNFRSF1A:TRADD:TRAF2"/> <bbox w="216.0" h="85.0" x="2445.9963" y="1647.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s18_mpk1_mpk1_sa436"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNFRSF1A-associated via death domain HUGO:TRADD HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TRADD"/> <bbox w="50.0" h="25.0" x="2567.4963" y="1655.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s19_mpk1_mpk1_sa437"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2504.4963" y="1680.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s20_mpk1_mpk1_sa438"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: receptor (TNFRSF)-interacting serine-threonine kinase 1 HUGO:RIPK1 HGNC:10019 ENTREZ:8737 UNIPROT:Q13546 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TNF treatment is thought to result in the formation of a TRADD-RIP-TRAF2 complex at the membrane. PMID:11274345 References_end</body> </html> </notes> <label text="RIPK1"/> <bbox w="50.0" h="25.0" x="2554.4963" y="1680.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s831_mpk1_mpk1_sa593"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1A TNFR1 HUGO:TNFRSF1A HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1A"/> <bbox w="70.0" h="25.0" x="2496.4546" y="1656.0"/> <glyph class="unit of information" id="_db03f7ae-22e3-47b2-86d5-d363581a63a0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2508.9546" y="1651.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s15_mpk1_mpk1_csa72" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TNFRSF1A:TRADD:TRAF2 Identifiers_end</body> </html> </notes> <label text="TNFRSF1A:TRADD:TRAF2"/> <bbox w="180.0" h="113.0" x="2451.9963" y="1501.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s1_mpk1_mpk1_sa430"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNFRSF1A-associated via death domain HUGO:TRADD HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TRADD"/> <bbox w="55.0" h="25.0" x="2512.9963" y="1535.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s2_mpk1_mpk1_sa431"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1A TNFR1 HUGO:TNFRSF1A HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1A"/> <bbox w="70.0" h="25.0" x="2507.9963" y="1511.0"/> <glyph class="unit of information" id="_9abb73ee-fb8b-4721-82ae-b26d697f571e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2520.4963" y="1506.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s3_mpk1_mpk1_sa432"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2514.9963" y="1561.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s16_mpk1_mpk1_csa73" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TNFRSF1A:TRADD Identifiers_end</body> </html> </notes> <label text="TNFRSF1A:TRADD"/> <bbox w="126.0" h="83.0" x="2421.9963" y="1392.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s7_mpk1_mpk1_sa434"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNFRSF1A-associated via death domain HUGO:TRADD HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TRADD"/> <bbox w="50.0" h="25.0" x="2459.4963" y="1424.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s830_mpk1_mpk1_sa592"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: tumor necrosis factor receptor superfamily member 1A TNFR1 HUGO:TNFRSF1A HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins. PMID:11274345 References_end</body> </html> </notes> <label text="TNFRSF1A"/> <bbox w="70.0" h="25.0" x="2450.0" y="1401.0"/> <glyph class="unit of information" id="_5997f1e3-b729-494f-aabd-4804947302e7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2462.5" y="1396.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s49_mpk1_mpk1_csa80" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TGFBR1:TGFBR2 Identifiers_end</body> </html> </notes> <label text="TGFBR1:TGFBR2"/> <bbox w="130.0" h="64.0" x="3419.9963" y="1314.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s46_mpk1_mpk1_sa453"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor 1 "transforming growth factor beta receptor I (activin A receptor type II-like kinase 53kD)" HUGO:TGFBR1 HGNC:11772 ENTREZ:7046 UNIPROT:P36897 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR1"/> <bbox w="55.0" h="25.0" x="3430.9963" y="1325.0"/> <glyph class="unit of information" id="_4ea1af92-9f2a-40d7-9123-21f4c106d0de"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3435.9963" y="1320.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s47_mpk1_mpk1_sa454"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor II (70/80kDa) MFS2 "transforming growth factor beta receptor II (70-80kD)" HUGO:TGFBR2 HGNC:11773 ENTREZ:7048 UNIPROT:P37173 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR2"/> <bbox w="55.0" h="25.0" x="3485.9963" y="1326.0"/> <glyph class="unit of information" id="_ab15a528-3969-486a-98ab-a3980c795b93"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3490.9963" y="1321.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1000_mpk1_mpk1_csa76" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TAB*:TGFBR1:TGFBR2 Identifiers_end</body> </html> </notes> <label text="TAB*:TGFBR1:TGFBR2"/> <bbox w="143.0" h="81.0" x="3285.9963" y="1619.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s728_mpk1_mpk1_sa443"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TGF-beta activated kinase 1/MAP3K7 binding protein 1 MAP3K7IP1 "mitogen-activated protein kinase kinase kinase 7 interacting protein 1" HUGO:TAB1 HGNC:18157 ENTREZ:10454 UNIPROT:Q15750 TGF-beta activated kinase 1/MAP3K7 binding protein 2 MAP3K7IP2 "mitogen-activated protein kinase kinase kinase 7 interacting protein 2" HUGO:TAB2 HGNC:17075 ENTREZ:23118 UNIPROT:Q9NYJ8 TGF-beta activated kinase 1/MAP3K7 binding protein 3 MAP3K7IP3 "mitogen-activated protein kinase kinase kinase 7 interacting protein 3" HUGO:TAB3 HGNC:30681 ENTREZ:257397 UNIPROT:Q8N5C8 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TAK1 is the only MAP3K that requires the adapter proteins TAB123 for its activation. PMID:20060931 References_end</body> </html> </notes> <label text="TAB*"/> <bbox w="50.0" h="25.0" x="3301.163" y="1650.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s835_mpk1_mpk1_sa597"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor 1 "transforming growth factor beta receptor I (activin A receptor type II-like kinase 53kD)" HUGO:TGFBR1 HGNC:11772 ENTREZ:7046 UNIPROT:P36897 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR1"/> <bbox w="55.0" h="25.0" x="3301.2727" y="1629.0"/> <glyph class="unit of information" id="_62ea3e7e-dca8-4ab8-983f-a00ce0d3f00b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3306.2727" y="1624.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s55_mpk1_mpk1_sa598"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: transforming growth factor beta receptor II (70/80kDa) MFS2 "transforming growth factor beta receptor II (70-80kD)" HUGO:TGFBR2 HGNC:11773 ENTREZ:7048 UNIPROT:P37173 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled). Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta. PMID:20060931 PMID:21614932 References_end</body> </html> </notes> <label text="TGFBR2"/> <bbox w="55.0" h="25.0" x="3357.2727" y="1630.0"/> <glyph class="unit of information" id="_e823a417-2438-4391-812c-17ec77473be3"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3362.2727" y="1625.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s981_mpk1_mpk1_csa31" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:RTK*:SRC Identifiers_end</body> </html> </notes> <label text="RTK*:SRC"/> <bbox w="72.0" h="88.0" x="198.0" y="1403.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s273_mpk1_mpk1_sa164"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 GENECARDS:SRC REACTOME:402877 KEGG:6714 ATLASONC:SRCID448ch20q11 WIKI:SRC Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end</body> </html> </notes> <label text="SRC"/> <bbox w="50.0" h="25.0" x="207.0" y="1438.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s820_mpk1_mpk1_sa582"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="208.27272" y="1417.0"/> <glyph class="state variable" id="_f5321eac-0dbb-43ce-96be-c326882f6f21"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="253.27272" y="1429.6776"/> </glyph> <glyph class="state variable" id="_d5e2973a-53ba-4be1-aca2-453878bfa86c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="253.27272" y="1429.6776"/> </glyph> <glyph class="state variable" id="_9803efb0-8fbd-4569-8afc-a897e5ee6141"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="253.27272" y="1424.5"/> </glyph> <glyph class="unit of information" id="_353967c9-5587-49c8-b8bd-b7ddf09cfb3e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="210.77272" y="1412.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s987_mpk1_mpk1_csa32" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:PLCG1:RTK*:SRC Identifiers_end</body> </html> </notes> <label text="PLCG1:RTK*:SRC"/> <bbox w="113.0" h="115.0" x="215.0" y="1521.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s284_mpk1_mpk1_sa173"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end Identifiers_begin: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC1 "v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog" HUGO:SRC HGNC:11283 ENTREZ:6714 UNIPROT:P12931 GENECARDS:SRC REACTOME:402877 KEGG:6714 ATLASONC:SRCID448ch20q11 WIKI:SRC Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: Many activated RTKs induce the Src-dependent activation of PLCG PMID:17496910 References_end</body> </html> </notes> <label text="SRC"/> <bbox w="50.0" h="25.0" x="245.0" y="1557.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s285_mpk1_mpk1_sa174"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: phospholipase C gamma 1 "phospholipase C gamma 1 (formerly subtype 148)" PLC1 HUGO:PLCG1 HGNC:9065 ENTREZ:5335 UNIPROT:P19174 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In response to Src-dependent activation of PLCG1 RasGRP1 translocated to the Golgi where it activated Ras. PMID:12845332 References_end</body> </html> </notes> <label text="PLCG1"/> <bbox w="50.0" h="25.0" x="245.0" y="1582.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s821_mpk1_mpk1_sa583"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="245.27272" y="1534.0"/> <glyph class="state variable" id="_23401b8b-0535-4420-b5ed-7545fc8f7012"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="290.2727" y="1546.6776"/> </glyph> <glyph class="state variable" id="_0024d82d-b012-469b-9d9c-0ef95b330bb3"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="290.2727" y="1546.6776"/> </glyph> <glyph class="state variable" id="_9fa774c5-c1ee-40d8-937a-69086107bf23"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="290.2727" y="1541.5"/> </glyph> <glyph class="unit of information" id="_7b146f29-e885-4544-acd9-ded81736812c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="247.77272" y="1529.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s32_mpk1_mpk1_csa77" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL1R1:MYD88 Identifiers_end</body> </html> </notes> <label text="IL1R1:MYD88"/> <bbox w="97.0" h="81.0" x="3071.9963" y="1437.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s33_mpk1_mpk1_sa445"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: myeloid differentiation primary response 88 "myeloid differentiation primary response gene (88)" HUGO:MYD88 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: The IL-1R/IL-1RAcP heterodimer recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="MYD88"/> <bbox w="59.0" h="24.0" x="3090.4963" y="1468.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s833_mpk1_mpk1_sa596"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 1 receptor type I IL1R IL1RA HUGO:IL1R1 HGNC:5993 ENTREZ:3554 UNIPROT:P14778 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IL-1 likely requires TRAF6 to signal to the SAPKs. IL-1 binding to its receptor (IL-1R) triggers heterodimerisation of IL-1R with IL-1RAcP (not modelled) a transmembrane protein necessary for IL-1 signal transduction. The IL-1R/IL-1RAcP heterodimer then recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="IL1R1"/> <bbox w="50.0" h="25.0" x="3095.4546" y="1446.0"/> <glyph class="unit of information" id="_e1c9e259-6b8c-4aa2-9ea1-1cc160d1727a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3097.9546" y="1441.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s705_mpk1_mpk1_csa78" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL1R1:IRAK1:MYD88:TRAF6 Identifiers_end</body> </html> </notes> <label text="IL1R1:IRAK1:MYD88:TRAF6"/> <bbox w="190.0" h="85.0" x="3035.9963" y="1658.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s42_mpk1_mpk1_sa447"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: myeloid differentiation primary response 88 "myeloid differentiation primary response gene (88)" HUGO:MYD88 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: The IL-1R/IL-1RAcP heterodimer recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="MYD88"/> <bbox w="56.0" h="25.0" x="3076.4963" y="1692.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s40_mpk1_mpk1_sa448"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin-1 receptor-associated kinase 1 HUGO:IRAK1 HGNC:6112 ENTREZ:3654 UNIPROT:P51617 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Similar to RIP recruitment by TRADD the death domain of receptor-bound MyD88 binds IRAK1. PMID:11274345 References_end</body> </html> </notes> <label text="IRAK1"/> <bbox w="50.0" h="25.0" x="3132.4963" y="1692.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s41_mpk1_mpk1_sa449"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 6 E3 ubiquitin protein ligase "TNF receptor-associated factor 6" HUGO:TRAF6 HGNC:12036 ENTREZ:7189 UNIPROT:Q9Y4K3 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Upon recruitment to the IL-1R complex IRAK1 binds TRAF6 forming a MyD88-IRAK1-TRAF6 complex analogous to the TNFR-associated complex of TRADD RIP and TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF6"/> <bbox w="50.0" h="25.0" x="3128.4963" y="1666.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s832_mpk1_mpk1_sa594"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 1 receptor type I IL1R IL1RA HUGO:IL1R1 HGNC:5993 ENTREZ:3554 UNIPROT:P14778 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IL-1 likely requires TRAF6 to signal to the SAPKs. IL-1 binding to its receptor (IL-1R) triggers heterodimerisation of IL-1R with IL-1RAcP (not modelled) a transmembrane protein necessary for IL-1 signal transduction. The IL-1R/IL-1RAcP heterodimer then recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="IL1R1"/> <bbox w="50.0" h="25.0" x="3078.4546" y="1668.0"/> <glyph class="unit of information" id="_3f6afa60-2bb0-4e7b-9490-37c76f9a2425"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3080.9546" y="1663.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s999_mpk1_mpk1_csa79" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL1R1:IRAK1:MYD88 Identifiers_end</body> </html> </notes> <label text="IL1R1:IRAK1:MYD88"/> <bbox w="145.0" h="84.0" x="3068.9963" y="1552.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s36_mpk1_mpk1_sa451"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: myeloid differentiation primary response 88 "myeloid differentiation primary response gene (88)" HUGO:MYD88 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: The IL-1R/IL-1RAcP heterodimer recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="MYD88"/> <bbox w="59.0" h="25.0" x="3086.4963" y="1583.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s37_mpk1_mpk1_sa452"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin-1 receptor-associated kinase 1 HUGO:IRAK1 HGNC:6112 ENTREZ:3654 UNIPROT:P51617 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Similar to RIP recruitment by TRADD the death domain of receptor-bound MyD88 binds IRAK1. PMID:11274345 References_end</body> </html> </notes> <label text="IRAK1"/> <bbox w="50.0" h="25.0" x="3145.4963" y="1583.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s834_mpk1_mpk1_sa595"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 1 receptor type I IL1R IL1RA HUGO:IL1R1 HGNC:5993 ENTREZ:3554 UNIPROT:P14778 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IL-1 likely requires TRAF6 to signal to the SAPKs. IL-1 binding to its receptor (IL-1R) triggers heterodimerisation of IL-1R with IL-1RAcP (not modelled) a transmembrane protein necessary for IL-1 signal transduction. The IL-1R/IL-1RAcP heterodimer then recruits the death domain adapter protein MyD88. PMID:11274345 References_end</body> </html> </notes> <label text="IL1R1"/> <bbox w="50.0" h="25.0" x="3090.4546" y="1561.0"/> <glyph class="unit of information" id="_a33d6764-662f-4785-b24d-12ca6771fb4f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3092.9546" y="1556.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s989_mpk1_mpk1_csa6" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RTK*:SOS*"/> <bbox w="109.0" h="104.0" x="791.0" y="1387.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s764_mpk1_mpk1_sa26"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="819.5" y="1440.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s887_mpk1_mpk1_sa27"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="820.5" y="1415.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s888_mpk1_mpk1_sa32"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="821.5" y="1392.5"/> <glyph class="state variable" id="_e60cbcec-0054-4bf0-8c06-8eedd8548ee8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="866.5" y="1405.1776"/> </glyph> <glyph class="state variable" id="_23ce26b9-1088-4a58-ba3d-32471a8d3cd1"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="866.5" y="1405.1776"/> </glyph> <glyph class="state variable" id="_50caaf78-b699-4073-8a50-08a1513e8802"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="866.5" y="1400.0"/> </glyph> <glyph class="unit of information" id="_2ec9604d-cdc1-462d-b384-e101fa03d87c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="824.0" y="1387.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s991_mpk1_mpk1_csa3" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RAS*:RTK*:SOS*"/> <bbox w="143.0" h="103.0" x="876.0" y="1657.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s758_mpk1_mpk1_sa11"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="901.0" y="1713.0"/> <glyph class="state variable" id="_03a32025-6e7e-4b83-82c6-246395c79c74"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="893.5" y="1720.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s759_mpk1_mpk1_sa15"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="949.5" y="1715.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s760_mpk1_mpk1_sa30"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="950.5" y="1688.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s761_mpk1_mpk1_sa34"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="950.5" y="1665.5"/> <glyph class="state variable" id="_823cc8ac-9f45-436a-86f6-e1d0ab751574"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="995.5" y="1678.1776"/> </glyph> <glyph class="state variable" id="_26dfca1c-d21a-4832-a857-7687d486c2f6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="995.5" y="1678.1776"/> </glyph> <glyph class="state variable" id="_1f0ff98d-0c84-44e5-90ea-cb0ad634b239"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="995.5" y="1673.0"/> </glyph> <glyph class="unit of information" id="_82d1cceb-4290-47e5-869a-be3cc760b09b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="953.0" y="1660.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s992_mpk1_mpk1_csa68" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RAF1:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RAF1:RAS*:RTK*:SOS*"/> <bbox w="185.0" h="106.0" x="1150.0" y="1641.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s752_mpk1_mpk1_sa333"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1271.0" y="1674.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s753_mpk1_mpk1_sa334"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1270.0" y="1699.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s572_mpk1_mpk1_sa337"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="1166.0" y="1699.0"/> <glyph class="state variable" id="_a8cc4159-df92-443d-8152-f2b6a34326f9"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1158.5" y="1707.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s824_mpk1_mpk1_sa585"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1271.0" y="1651.0"/> <glyph class="state variable" id="_742a9d15-fd7e-4df3-a356-ad5c7f6a2e7a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1316.0" y="1663.6776"/> </glyph> <glyph class="state variable" id="_0eb6014a-bc72-4a54-a570-0f600a8047be"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1316.0" y="1663.6776"/> </glyph> <glyph class="state variable" id="_c84b5a3d-ee91-4d8a-ac5c-5a068f1a80e7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1316.0" y="1658.5"/> </glyph> <glyph class="unit of information" id="_6a7045dc-fccf-4920-9639-a66d6ef8010a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1273.5" y="1646.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s858_mpk1_mpk1_sa619"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1227.375" y="1698.5"/> <glyph class="state variable" id="_393a9e32-5d8c-4b46-8579-58fef0a14eff"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1219.875" y="1706.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s990_mpk1_mpk1_csa99" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:RAC1:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:RAC1:RTK*:SOS*"/> <bbox w="152.0" h="103.0" x="1168.9965" y="1393.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s621_mpk1_mpk1_sa522"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1248.4965" y="1421.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s622_mpk1_mpk1_sa523"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1248.4965" y="1445.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s624_mpk1_mpk1_sa524"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end Identifiers_begin: Ras-related C3 botulin toxin substrate 1 (rho family, small GTP binding protein Rac1 HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 GENECARDS:RAC1 REACTOME:404635 KEGG:5879 ATLASONC:GC_RAC1 WIKI:RAC1 ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:18000759 PMID:19151919 Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end</body> </html> Identifiers_begin: Ras-related C3 botulin toxin substrate 1 (rho family, small GTP binding protein Rac1 HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 GENECARDS:RAC1 REACTOME:404635 KEGG:5879 ATLASONC:GC_RAC1 WIKI:RAC1 ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:18000759 PMID:19151919 Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end</body> </html> Identifiers_begin: Ras-related C3 botulin toxin substrate 1 (rho family, small GTP binding protein Rac1 HUGO:RAC1 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 GENECARDS:RAC1 REACTOME:404635 KEGG:5879 ATLASONC:GC_RAC1 WIKI:RAC1 ras-related C3 botulinum toxin substrate 1 (rho family small GTP binding protein RAC1) Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:18000759 PMID:19151919 Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2). PMID:11274345 References_end</body> </html> </notes> <label text="RAC1"/> <bbox w="60.0" h="25.0" x="1194.4965" y="1445.0"/> <glyph class="state variable" id="_6a9a87e5-92ba-4ee1-86d8-7d08d59982b3"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1186.9965" y="1452.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s822_mpk1_mpk1_sa587"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1249.0" y="1401.0"/> <glyph class="state variable" id="_dba5ccf0-7364-4409-bc32-0dee5597ea9b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1294.0" y="1413.6776"/> </glyph> <glyph class="state variable" id="_e0dc7f31-61aa-44a0-8b9e-6ec331f14397"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1294.0" y="1413.6776"/> </glyph> <glyph class="state variable" id="_5993c183-2121-4e9f-a911-05fef9fb9533"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1294.0" y="1408.5"/> </glyph> <glyph class="unit of information" id="_00adca0a-82a5-4897-8168-dbaa2b3c4ebf"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1251.5" y="1396.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s997_mpk1_mpk1_csa64" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GPCR*:GRK* Identifiers_end</body> </html> </notes> <label text="GPCR*:GRK*"/> <bbox w="81.0" h="81.0" x="2197.0" y="1414.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s543_mpk1_mpk1_sa316"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2215.0" y="1447.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s871_mpk1_mpk1_sa590"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="66.0" h="26.0" x="2207.0" y="1426.0"/> <glyph class="state variable" id="_73143b31-e5e4-4f28-89a7-6265ff6307f4"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2199.5" y="1434.0"/> </glyph> <glyph class="unit of information" id="_1f232837-f76b-4f36-bb05-8ef2221f48f2"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2217.5" y="1421.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s26_mpk1_mpk1_csa81" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERN1:TRAF2 Identifiers_end</body> </html> </notes> <label text="ERN1:TRAF2"/> <bbox w="88.0" h="87.0" x="2895.9963" y="1498.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s28_mpk1_mpk1_sa455"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TNF receptor-associated factor 2 HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="TRAF2"/> <bbox w="50.0" h="25.0" x="2915.4963" y="1533.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s84_mpk1_mpk1_sa456"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: endoplasmic reticulum to nucleus signaling 1 "ER to nucleus signalling 1" HUGO:ERN1 HGNC:3449 ENTREZ:2081 UNIPROT:O75460 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: ER stress lead to the oligomerisation and activation of mammalian Ire1p (ERN1). ERN1 activation is likely to trigger binding and activation of TRAF2. PMID:11274345 References_end</body> </html> </notes> <label text="ERN1"/> <bbox w="50.0" h="25.0" x="2916.4963" y="1506.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s982_mpk1_mpk1_csa33" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DAG:RASGRP1 Identifiers_end</body> </html> </notes> <label text="DAG:RASGRP1"/> <bbox w="103.0" h="82.0" x="379.0" y="1406.0"/> <glyph class="simple chemical" id="mpk1_mpk1_s293_mpk1_mpk1_sa178"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Diacylglycerol CAS:N/A PUBCHEM:3914 CHEBI:17815 KEGGCOMPOUND:C00165 Identifiers_end Maps_Modules_begin: MODULE:MAPK Maps_Modules_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="394.0" y="1414.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s291_mpk1_mpk1_sa179"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="398.0" y="1439.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s988_mpk1_mpk1_csa34" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RASGRP1"/> <bbox w="141.0" h="85.0" x="449.5" y="1507.5"/> <glyph class="simple chemical" id="mpk1_mpk1_s890_mpk1_mpk1_sa181"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Diacylglycerol CAS:N/A PUBCHEM:3914 CHEBI:17815 KEGGCOMPOUND:C00165 Identifiers_end Maps_Modules_begin: MODULE:MAPK Maps_Modules_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="496.5" y="1517.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s891_mpk1_mpk1_sa182"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="500.5" y="1542.5"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s892_mpk1_mpk1_sa273"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="455.0" y="1526.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1001_mpk1_mpk1_csa35" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RASGRP1"/> <bbox w="144.0" h="84.0" x="394.0" y="2135.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s838_mpk1_mpk1_sa185"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="450.0" y="2168.0"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s839_mpk1_mpk1_sa274"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="402.44446" y="2151.4443"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s837_mpk1_mpk1_sa600"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Generic_begin: DAG Generic_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="446.125" y="2143.75"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s983_mpk1_mpk1_csa110" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:PKC* Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:PKC*"/> <bbox w="117.0" h="91.0" x="560.0" y="1385.0"/> <glyph class="simple chemical" id="mpk1_mpk1_s935_mpk1_mpk1_sa688"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Diacylglycerol CAS:N/A PUBCHEM:3914 CHEBI:17815 KEGGCOMPOUND:C00165 Identifiers_end Maps_Modules_begin: MODULE:MAPK Maps_Modules_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="600.0" y="1392.5"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s934_mpk1_mpk1_sa689"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="564.5" y="1406.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s936_mpk1_mpk1_sa690"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: protein kinase C alpha PKCA HUGO:PRKCA HGNC:9393 ENTREZ:5578 UNIPROT:P17252 protein kinase C beta PKCB PRKCB1 PRKCB2 "protein kinase C beta 1" HUGO:PRKCB HGNC:9395 ENTREZ:5579 UNIPROT:P05771 protein kinase C gamma PKCG SCA14 HUGO:PRKCG HGNC:9402 ENTREZ:5582 UNIPROT:P05129 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity. PMID:15567848 References_end Identifiers_begin: protein kinase C alpha PKCA HUGO:PRKCA HGNC:9393 ENTREZ:5578 UNIPROT:P17252 GENECARDS:PRKCA REACTOME:58197 KEGG:5578 ATLASONC:GC_PRKCA WIKI:PRKCA protein kinase C beta PKCB PRKCB1 PRKCB2 "protein kinase C beta 1" HUGO:PRKCB HGNC:9395 ENTREZ:5579 UNIPROT:P05771 GENECARDS:PRKCB REACTOME:58199 KEGG:5579 ATLASONC:GC_PRKCB WIKI:PRKCB protein kinase C gamma PKCG SCA14 HUGO:PRKCG HGNC:9402 ENTREZ:5582 UNIPROT:P05129 GENECARDS:PRKCG REACTOME:58205 KEGG:5582 ATLASONC:GC_PRKCG WIKI:PRKCG protein kinase C, delta HUGO:PRKCD HGNC:9399 ENTREZ:5580 UNIPROT:Q05655 GENECARDS:PRKCD REACTOME:58201 KEGG:5580 ATLASONC:PRKCDID42901ch3p21 WIKI:PRKCD protein kinase C, epsilon HUGO:PRKCE HGNC:9401 ENTREZ:5581 UNIPROT:Q02156 GENECARDS:PRKCE REACTOME:58203 KEGG:5581 ATLASONC:GC_PRKCE WIKI:PRKCE protein kinase C, eta HUGO:PRKCH HGNC:9403 ENTREZ:5583 UNIPROT:P24723 GENECARDS:PRKCH REACTOME:58209 KEGG:5583 ATLASONC:GC_PRKCH WIKI:PRKCH protein kinase C, iota HUGO:PRKCI HGNC:9404 ENTREZ:5584 UNIPROT:P41743 GENECARDS:PRKCI REACTOME:58207 KEGG:5584 ATLASONC:PRKCIID41857ch3q26 WIKI:PRKCI protein kinase C, theta HUGO:PRKCQ HGNC:9410 ENTREZ:5588 UNIPROT:Q04759 GENECARDS:PRKCQ REACTOME:58217 KEGG:5588 ATLASONC:GC_PRKCQ WIKI:PRKCQ Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity. PMID:15567848 PMID:11313945 PMID:11940581 Only PKC alpha and delta PMID:21386996 References_end</body> </html> Identifiers_begin: protein kinase C alpha PKCA HUGO:PRKCA HGNC:9393 ENTREZ:5578 UNIPROT:P17252 GENECARDS:PRKCA REACTOME:58197 KEGG:5578 ATLASONC:GC_PRKCA WIKI:PRKCA protein kinase C beta PKCB PRKCB1 PRKCB2 "protein kinase C beta 1" HUGO:PRKCB HGNC:9395 ENTREZ:5579 UNIPROT:P05771 GENECARDS:PRKCB REACTOME:58199 KEGG:5579 ATLASONC:GC_PRKCB WIKI:PRKCB protein kinase C gamma PKCG SCA14 HUGO:PRKCG HGNC:9402 ENTREZ:5582 UNIPROT:P05129 GENECARDS:PRKCG REACTOME:58205 KEGG:5582 ATLASONC:GC_PRKCG WIKI:PRKCG protein kinase C, delta HUGO:PRKCD HGNC:9399 ENTREZ:5580 UNIPROT:Q05655 GENECARDS:PRKCD REACTOME:58201 KEGG:5580 ATLASONC:PRKCDID42901ch3p21 WIKI:PRKCD protein kinase C, epsilon HUGO:PRKCE HGNC:9401 ENTREZ:5581 UNIPROT:Q02156 GENECARDS:PRKCE REACTOME:58203 KEGG:5581 ATLASONC:GC_PRKCE WIKI:PRKCE protein kinase C, eta HUGO:PRKCH HGNC:9403 ENTREZ:5583 UNIPROT:P24723 GENECARDS:PRKCH REACTOME:58209 KEGG:5583 ATLASONC:GC_PRKCH WIKI:PRKCH protein kinase C, iota HUGO:PRKCI HGNC:9404 ENTREZ:5584 UNIPROT:P41743 GENECARDS:PRKCI REACTOME:58207 KEGG:5584 ATLASONC:PRKCIID41857ch3q26 WIKI:PRKCI protein kinase C, theta HUGO:PRKCQ HGNC:9410 ENTREZ:5588 UNIPROT:Q04759 GENECARDS:PRKCQ REACTOME:58217 KEGG:5588 ATLASONC:GC_PRKCQ WIKI:PRKCQ Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity. PMID:15567848 PMID:11313945 PMID:11940581 Only PKC alpha and delta PMID:21386996 References_end</body> </html> </notes> <label text="PKC*"/> <bbox w="50.0" h="25.0" x="610.0" y="1418.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s993_mpk1_mpk1_csa4" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:GRB2:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:GRB2:RAS*:RTK*:SOS*"/> <bbox w="189.0" h="103.0" x="1430.0" y="1437.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s61_mpk1_mpk1_sa38"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1555.5" y="1469.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s756_mpk1_mpk1_sa39"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1555.5" y="1493.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s143_mpk1_mpk1_sa49"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1446.5" y="1493.5"/> <glyph class="state variable" id="_9bedcf35-09ed-4d1b-aa2a-0cf26a648f40"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1439.0" y="1501.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s823_mpk1_mpk1_sa586"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1557.0" y="1448.0"/> <glyph class="state variable" id="_e1483822-40ad-4819-bf37-b1f63828f79c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1602.0" y="1460.6776"/> </glyph> <glyph class="state variable" id="_9cd1ec45-d732-4215-a82a-5e0d6e799fda"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1602.0" y="1460.6776"/> </glyph> <glyph class="state variable" id="_70bd4e99-44f8-405b-a22b-a1a85ecb75f0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1602.0" y="1455.5"/> </glyph> <glyph class="unit of information" id="_4f842124-f862-444c-ba7f-c1b399bb8e64"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1559.5" y="1443.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s857_mpk1_mpk1_sa618"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1508.375" y="1493.0"/> <glyph class="state variable" id="_a7a5fb16-7a5b-49b4-aa91-e59196915259"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1500.875" y="1500.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s995_mpk1_mpk1_csa11" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:GRB2:KSR1:MEK*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:GRB2:KSR1:MEK*:RAS*:RTK*:SOS*"/> <bbox w="259.0" h="168.0" x="1806.5" y="1405.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s86_mpk1_mpk1_sa56"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1974.0" y="1437.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s87_mpk1_mpk1_sa57"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1974.0" y="1462.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s82_mpk1_mpk1_sa62"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="41.0" h="77.0" x="1826.5" y="1463.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s83_mpk1_mpk1_sa63"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="1871.5" y="1488.0"/> <glyph class="state variable" id="_abc450e2-ee67-48c0-9912-6d8545dcde37"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1864.0" y="1500.333"/> </glyph> <glyph class="state variable" id="_79bea096-e819-4da9-873d-201e234cdea1"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1864.0" y="1491.451"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s144_mpk1_mpk1_sa59"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1867.0" y="1463.0"/> <glyph class="state variable" id="_5932bf57-ff63-48bb-9c7e-5df3d0902257"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1859.5" y="1471.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s825_mpk1_mpk1_sa584"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1975.0" y="1416.0"/> <glyph class="state variable" id="_d425768b-9be7-4aec-adf4-013788532af8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2020.0" y="1428.6776"/> </glyph> <glyph class="state variable" id="_ab211c4d-a630-4aec-a65d-b71f826fd305"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2020.0" y="1428.6776"/> </glyph> <glyph class="state variable" id="_7da58891-5b76-4396-adc6-ead8450a9179"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2020.0" y="1423.5"/> </glyph> <glyph class="unit of information" id="_971f89c4-7241-492d-9d1f-906c789725db"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1977.5" y="1411.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s88_mpk1_mpk1_sa620"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1926.125" y="1462.0"/> <glyph class="state variable" id="_5b353ab0-9077-4806-8409-e138c58ce5e6"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1918.625" y="1469.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s996_mpk1_mpk1_csa24" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:GRB2:KSR1-NTER*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:GRB2:KSR1-NTER*:RAS*:RTK*:SOS*"/> <bbox w="257.0" h="135.0" x="1830.0" y="1614.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s207_mpk1_mpk1_sa125"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="2006.5" y="1645.125"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s210_mpk1_mpk1_sa126"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="2005.5" y="1669.125"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s209_mpk1_mpk1_sa128"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1893.5" y="1669.875"/> <glyph class="state variable" id="_af14ec19-7cbe-4e2b-9625-fd300f45e879"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1886.0" y="1677.875"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s211_mpk1_mpk1_sa130"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is cleaved by CASPASE3 in two regions: the C-ter region which mediates MEK binding and the N-ter region which contains the ERK binding site and the C1 domain required for plasma membrane localisation PMID:17613518 References_end</body> </html> </notes> <label text="KSR1-NTER*"/> <bbox w="116.0" h="25.0" x="1885.0" y="1695.0"/> <glyph class="unit of information" id="_47efb3d3-baaa-4d68-abb4-bb60a5afaa5a"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="1918.0" y="1690.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s827_mpk1_mpk1_sa588"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="2007.1818" y="1624.0"/> <glyph class="state variable" id="_8f57c748-f60a-46b0-bcc4-e600fcca032c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2052.1816" y="1636.6776"/> </glyph> <glyph class="state variable" id="_f76d2919-7819-4940-8637-faeeb6620aca"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2052.1816" y="1636.6776"/> </glyph> <glyph class="state variable" id="_7fe8939b-d1c9-407c-85b0-908adfd6cb78"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2052.1816" y="1631.5"/> </glyph> <glyph class="unit of information" id="_d5580ccc-5268-4519-8c33-bcc0dbd648a5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2009.6818" y="1619.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s208_mpk1_mpk1_sa632"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1957.125" y="1669.5"/> <glyph class="state variable" id="_ace4bd27-f7d3-4f6d-b751-b2d5a8d706a4"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1949.625" y="1677.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s994_mpk1_mpk1_csa12" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BRAF:ERK*:GRB2:KSR1:MEK*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="BRAF:ERK*:GRB2:KSR1:MEK*:RAS*:RTK*:SOS*"/> <bbox w="286.0" h="163.0" x="1391.5" y="1600.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s866_mpk1_mpk1_sa621"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1591.625" y="1608.0"/> <glyph class="state variable" id="_9eff1389-7070-40bb-bbee-9b29ec90989b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1636.625" y="1620.6776"/> </glyph> <glyph class="state variable" id="_88988dbc-7411-4748-af35-01493b032f9e"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1636.625" y="1620.6776"/> </glyph> <glyph class="state variable" id="_8ac615fe-2e98-44cd-8b03-184bc1504d1a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1636.625" y="1615.5"/> </glyph> <glyph class="unit of information" id="_46b80b94-be1e-4f6e-8ba0-d51c4dac3fdc"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1594.125" y="1603.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s860_mpk1_mpk1_sa622"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1590.625" y="1629.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s861_mpk1_mpk1_sa623"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1590.625" y="1654.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s865_mpk1_mpk1_sa627"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="41.0" h="77.0" x="1443.125" y="1655.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s867_mpk1_mpk1_sa628"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="66.0" h="26.0" x="1488.0" y="1705.75"/> <glyph class="state variable" id="_a40a3458-dea0-461e-af26-2d038a7c9c90"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.5" y="1718.2809"/> </glyph> <glyph class="state variable" id="_0e5a3efa-d8d2-4a10-9392-ba5a2c6ff1d4"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.5" y="1708.6022"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s868_mpk1_mpk1_sa629"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="1487.625" y="1681.25"/> <glyph class="state variable" id="_b79f96fb-47f0-4f08-8c54-e86fa9ab1874"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.125" y="1693.583"/> </glyph> <glyph class="state variable" id="_de176abb-e7f6-4110-9dd6-f1030fedd7b3"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1480.125" y="1684.701"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s869_mpk1_mpk1_sa630"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: v-raf murine sarcoma viral oncogene homolog B1 HUGO:BRAF HGNC:1097 ENTREZ:673 UNIPROT:P15056 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: B-Raf is the MAPKKK for ERK cascade on plasma membrane. It is phosphorylated by RasGTP and phosphorylates MEK1/2 on plasma membrane. PMID:17496910 References_end</body> </html> </notes> <label text="BRAF"/> <bbox w="66.0" h="26.0" x="1483.125" y="1656.25"/> <glyph class="state variable" id="_98f6f7ea-b30e-482d-a29d-f977db63ba9a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1475.625" y="1664.25"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s870_mpk1_mpk1_sa631"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1542.125" y="1655.0"/> <glyph class="state variable" id="_5742a898-0591-45a3-927a-56e12b3caf4e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1534.625" y="1662.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s953_mpk1_mpk1_csa112" compartmentRef="mpk1_mpk1_c7_mpk1_mpk1_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BAD:BCL2 Identifiers_end</body> </html> </notes> <label text="BAD:BCL2"/> <bbox w="80.0" h="85.0" x="1177.0" y="1867.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s954_mpk1_mpk1_sa703"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: BCL2-associated agonist of cell death HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release. PMID:12107820 References_end Identifiers_begin: BCL2-associated agonist of cell death HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 GENECARDS:BAD REACTOME:50663 KEGG:572 ATLASONC:BADID130ch11q13 WIKI:BAD Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:APOPTOSIS_GENES MAP:apoptosis / MODULE:MITOCH_METABOLISM MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release. PMID:12107820 PMID:10949026 PMID:19641503 References_end</body> </html> Identifiers_begin: BCL2-associated agonist of cell death HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 GENECARDS:BAD REACTOME:50663 KEGG:572 ATLASONC:BADID130ch11q13 WIKI:BAD Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:APOPTOSIS_GENES MAP:apoptosis / MODULE:MITOCH_METABOLISM MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release. PMID:12107820 PMID:10949026 PMID:19641503 References_end</body> </html> </notes> <label text="BAD"/> <bbox w="50.0" h="25.0" x="1192.0" y="1879.5"/> <glyph class="state variable" id="_ac8f8ca4-2f77-417a-a3e5-65d262dd8b2e"> <state value="" variable="S112"/> <bbox w="30.0" h="10.0" x="1177.3079" y="1874.5"/> </glyph> <glyph class="state variable" id="_1340fb6c-6c64-4df8-9710-b16632532553"> <state value="" variable="S136"/> <bbox w="30.0" h="10.0" x="1227.0" y="1874.6343"/> </glyph> <glyph class="state variable" id="_8a29a6f6-0f50-438a-910f-6e8c3987ab10"> <state value="" variable="S155"/> <bbox w="30.0" h="10.0" x="1226.6136" y="1899.5"/> </glyph> <glyph class="state variable" id="_d042000c-3238-4732-91df-9140505db329"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1187.0" y="1887.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s955_mpk1_mpk1_sa704"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: B-cell CLL/lymphoma 2 HUGO:BCL2 HGNC:990 ENTREZ:596 UNIPROT:P10415 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: BCL2 protein can target Raf-1 (C-Raf) to mitochondria. PMID:8929532 References_end</body> </html> </notes> <label text="BCL2"/> <bbox w="50.0" h="25.0" x="1192.0" y="1904.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s978_mpk1_mpk1_csa60" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MEK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="MEK*:β-Arrestin2*"/> <bbox w="115.0" h="119.0" x="2683.0" y="1881.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s513_mpk1_mpk1_sa292"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="76.0" x="2746.0" y="1889.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s514_mpk1_mpk1_sa293"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2698.0" y="1918.0"/> <glyph class="state variable" id="_a373f1f1-41b6-48e1-93e2-01c516601b97"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2693.0" y="1929.6664"/> </glyph> <glyph class="state variable" id="_4123112a-e14e-46b7-945d-4198d39c8cd8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2693.0" y="1921.1261"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s998_mpk1_mpk1_csa46" compartmentRef="mpk1_mpk1_c2_mpk1_mpk1_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GPCR*:GRK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="GPCR*:GRK*:β-Arrestin2*"/> <bbox w="129.0" h="159.0" x="2228.0" y="1560.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s480_mpk1_mpk1_sa237"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="76.0" x="2269.0" y="1618.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s537_mpk1_mpk1_sa312"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2268.5" y="1591.3334"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s828_mpk1_mpk1_sa591"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="66.0" h="26.0" x="2260.0908" y="1568.0"/> <glyph class="state variable" id="_5ae55e27-8411-4a2b-ae2f-91e00b07429a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2252.5908" y="1576.0"/> </glyph> <glyph class="unit of information" id="_06657ec5-5cdc-4f32-b485-4668262f0d15"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2270.5908" y="1563.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s984_mpk1_mpk1_csa66" compartmentRef="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:β-Arrestin2*"/> <bbox w="146.0" h="119.0" x="2299.0" y="2122.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s550_mpk1_mpk1_sa319"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="77.0" x="2375.5" y="2132.3333"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s551_mpk1_mpk1_sa320"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2326.5" y="2161.3333"/> <glyph class="state variable" id="_d5cba11a-e3aa-41b0-af2b-0bae5c1cfe7e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2172.9995"/> </glyph> <glyph class="state variable" id="_a9151b7d-5061-4283-a57c-47e7f1b49638"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2164.4592"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s552_mpk1_mpk1_sa321"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2326.5" y="2186.3333"/> <glyph class="state variable" id="_efcef904-7f4f-4261-b434-4d30a5352f99"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2198.19"/> </glyph> <glyph class="state variable" id="_539630c2-0764-42cb-81bd-cef35d8384ea"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2319.0" y="2188.8833"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s985_mpk1_mpk1_csa67" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:β-Arrestin2*"/> <bbox w="140.0" h="116.0" x="2389.0" y="2306.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s803_mpk1_mpk1_sa560"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="77.0" x="2462.0" y="2314.2727"/> </glyph> <glyph class="macromolecule multimer" id="mpk1_mpk1_s804_mpk1_mpk1_sa561"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - ERK represents both ERK1 and ERK2 because it is not completely clear when the two isoforms behave differently. This also happens for the activation on late endosomes: it is known that only ERK1 is activated there, however when ERK1 reaches nucleus, it behaves like ERK2. - Once activated, ERK may either keep being in complex with its activators and scaffolds, or be released in the cytoplasm. In the latter case, it may either dimerise, being able to activate its cytoplasmic targets, or not, being able to translocate to the nucleus. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2414.75" y="2369.7727"/> <glyph class="unit of information" id="_caba5678-c407-4e95-bf44-304415875034"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="2429.75" y="2364.7727"/> </glyph> <glyph class="state variable" id="_4e553ef9-0580-43b2-8c30-331c0dcbe10a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2407.25" y="2381.6294"/> </glyph> <glyph class="state variable" id="_1685e26d-bb19-4a32-8141-4904dc394645"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2407.25" y="2372.3228"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s805_mpk1_mpk1_sa563"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2413.0417" y="2342.3862"/> <glyph class="state variable" id="_a23a6b35-fd8f-4413-803b-0befbeccc5a8"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2405.5417" y="2354.0525"/> </glyph> <glyph class="state variable" id="_b9dd0927-8266-4096-80c7-8d84540ee1ce"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2405.5417" y="2345.5122"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1002_mpk1_mpk1_csa37" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RAS*:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RAS*:RASGRP1"/> <bbox w="181.0" h="110.0" x="187.5" y="2281.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s483_mpk1_mpk1_sa195"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="251.0" y="2316.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s485_mpk1_mpk1_sa197"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="267.0" y="2341.5"/> <glyph class="state variable" id="_f46703b5-214a-4029-99b4-da2e3c29cb62"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="259.5" y="2349.0"/> </glyph> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s489_mpk1_mpk1_sa276"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="203.44444" y="2299.2222"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s842_mpk1_mpk1_sa602"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: DAG Identifiers_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="249.125" y="2292.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1003_mpk1_mpk1_csa38" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Ca2+:DAG:RAF1:RAS*:RASGRP1 Identifiers_end</body> </html> </notes> <label text="Ca2+:DAG:RAF1:RAS*:RASGRP1"/> <bbox w="226.0" h="90.0" x="176.0" y="2525.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s321_mpk1_mpk1_sa206"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: RAS guanyl releasing protein 1 (calcium and DAG-regulated) HUGO:RASGRP1 HGNC:9878 ENTREZ:10125 UNIPROT:O95267 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGRP1 specifically activates H-Ras in the Golgi. It is localised in the cytosol in quiescent cells. After PMA stimulus at first it moves to the PM and then shifts towards other subcellular compartments like the Golgi apparatus. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+ in a manner analogous to members of the PKC family. PMID:12782630 PMID:17496910 Activation of PKC: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="RASGRP1"/> <bbox w="64.0" h="25.0" x="243.5" y="2561.0"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s490_mpk1_mpk1_sa277"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Ca2+ CAS:N/A PUBCHEM:N/A CHEBI:39124 KEGGCOMPOUND:N/A Identifiers_end References_begin: Calcium liberated from internal stores by IP3 acts on the calcium- and DAG-sensitive RasGRP1 and causes it to translocate to the Golgi. PMID:16488589 References_end</body> </html> </notes> <label text="Ca2+"/> <bbox w="61.0" h="38.0" x="195.44444" y="2543.2222"/> </glyph> <glyph class="simple chemical" id="mpk1_mpk1_s320_mpk1_mpk1_sa601"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Generic_begin: DAG Generic_end References_begin: DAG activates the C1-domain of RasGRP1. PLCG acts on PIP2 in the PM to produce DAG and IP3. RasGRP1 is a C1-domain containing protein that is activated by DAG and Ca2+, in a manner analogous to members of the PKC family. PMID:17496910, PMID:16488589, PMID:17496910 DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) ??? a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html References_end</body> </html> </notes> <label text="DAG"/> <bbox w="70.0" h="25.0" x="239.125" y="2537.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s843_mpk1_mpk1_sa603"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="311.375" y="2537.0"/> <glyph class="state variable" id="_74e30b57-ae43-435e-82f3-bfb5a6f1e544"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="303.875" y="2544.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s844_mpk1_mpk1_sa604"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="309.375" y="2563.0"/> <glyph class="state variable" id="_95c288a1-a3ee-4469-8b75-f8f20eb3c62d"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="301.875" y="2571.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1004_mpk1_mpk1_csa41" compartmentRef="mpk1_mpk1_c5_mpk1_mpk1_ca5"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:SEF*"/> <bbox w="112.0" h="87.0" x="425.0" y="2436.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s339_mpk1_mpk1_sa217"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="50.0" h="25.0" x="436.875" y="2446.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s340_mpk1_mpk1_sa215"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="474.26135" y="2446.1592"/> <glyph class="state variable" id="_7b125ca8-26a3-491d-97a3-4024fa4013b9"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.26135" y="2457.8254"/> </glyph> <glyph class="state variable" id="_c6d7a1f4-22c4-42ac-9b8b-24fc7248c93a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.26135" y="2449.2852"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s346_mpk1_mpk1_sa224"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="474.875" y="2471.75"/> <glyph class="state variable" id="_5f5a6d29-7887-4971-903a-c959036db6d7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.875" y="2483.6067"/> </glyph> <glyph class="state variable" id="_ac4e32fe-5748-49f9-acdd-d4ea5a60fba0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="469.875" y="2474.3"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1005_mpk1_mpk1_csa43" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:SEF*"/> <bbox w="126.0" h="87.0" x="677.0" y="2436.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s343_mpk1_mpk1_sa221"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="50.0" h="25.0" x="693.875" y="2445.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s344_mpk1_mpk1_sa222"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="730.26135" y="2445.6592"/> <glyph class="state variable" id="_0387c67c-4095-480e-8220-11ab5beb7304"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="722.76135" y="2457.3254"/> </glyph> <glyph class="state variable" id="_f9bfd5a4-8698-42ae-a0e2-8d42e1f7bdd6"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="722.76135" y="2448.7852"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s345_mpk1_mpk1_sa223"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="728.98865" y="2471.8408"/> <glyph class="state variable" id="_d11b153a-c373-48bb-a1e7-5111f4343efc"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="721.48865" y="2483.6975"/> </glyph> <glyph class="state variable" id="_d5846865-16d6-4d0b-8005-0ff2fd7720d5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="721.48865" y="2474.3909"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1006_mpk1_mpk1_csa63" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="ERK*:MEK*:SEF*"/> <bbox w="126.0" h="89.0" x="697.0" y="2565.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s533_mpk1_mpk1_sa308"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="66.0" h="26.0" x="717.5" y="2575.8335"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s534_mpk1_mpk1_sa309"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="753.5" y="2577.8335"/> <glyph class="state variable" id="_af469740-e1e1-4791-8034-45b4ea5811d0"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.0" y="2590.1665"/> </glyph> <glyph class="state variable" id="_48e30b55-e367-4de8-b272-0ea8ecdcb26e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.0" y="2581.2847"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="mpk1_mpk1_s535_mpk1_mpk1_sa310"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - ERK represents both ERK1 and ERK2 because it is not completely clear when the two isoforms behave differently. This also happens for the activation on late endosomes: it is known that only ERK1 is activated there, however when ERK1 reaches nucleus, it behaves like ERK2. - Once activated, ERK may either keep being in complex with its activators and scaffolds, or be released in the cytoplasm. In the latter case, it may either dimerise, being able to activate its cytoplasmic targets, or not, being able to translocate to the nucleus. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="66.0" h="26.0" x="753.9167" y="2603.3335"/> <glyph class="unit of information" id="_2233a7b4-a468-4b92-8594-550d194c07f6"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="776.9167" y="2598.3335"/> </glyph> <glyph class="state variable" id="_10000386-760f-4a04-8f59-e8d7690e1590"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.4167" y="2615.8645"/> </glyph> <glyph class="state variable" id="_8b1ea434-92e9-4659-9e6c-f47562f7afe8"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="746.4167" y="2606.1855"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1007_mpk1_mpk1_csa58" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MEK*:SEF* Identifiers_end</body> </html> </notes> <label text="MEK*:SEF*"/> <bbox w="104.0" h="93.0" x="633.0" y="2157.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s802_mpk1_mpk1_sa558"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: interleukin 17 receptor D HUGO:IL17RD HGNC:17616 ENTREZ:54756 UNIPROT:Q8NFM7 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins. Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked. PMID:19565474 PMID:19565474 References_end</body> </html> </notes> <label text="SEF*"/> <bbox w="37.0" h="58.0" x="640.2727" y="2168.318"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s855_mpk1_mpk1_sa617"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="37.0" h="58.0" x="678.625" y="2168.0"/> <glyph class="state variable" id="_e88b8d87-7898-4a5a-9481-405d4e58e863"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="673.625" y="2201.666"/> </glyph> <glyph class="state variable" id="_e3093863-b16a-4bb9-a59e-ba894a1cb120"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="673.625" y="2181.8525"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1008_mpk1_mpk1_csa113" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GAB1:GRB2 Identifiers_end</body> </html> </notes> <label text="GAB1:GRB2"/> <bbox w="80.0" h="84.0" x="706.5" y="1997.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s970_mpk1_mpk1_sa713"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="725.5" y="2005.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s971_mpk1_mpk1_sa714"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 GENECARDS:GAB1 REACTOME:147726 ATLASONC:GC_GAB1 WIKI:GAB1 GRB2-associated binding protein 2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:11313945 PMID:11940581 References_end</body> </html> </notes> <label text="GAB1"/> <bbox w="50.0" h="25.0" x="725.5" y="2030.5"/> <glyph class="state variable" id="_8d860e18-294b-4d55-9bfe-2cc5ac05ace1"> <state value="" variable="Y977"/> <bbox w="30.0" h="10.0" x="710.8078" y="2025.5"/> </glyph> <glyph class="state variable" id="_9b795641-6ebf-4850-9e34-3d23151a0b7d"> <state value="" variable="Y989"/> <bbox w="30.0" h="10.0" x="760.5" y="2025.6343"/> </glyph> <glyph class="state variable" id="_412cad16-c048-4108-9f3f-4393ca23ba42"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="718.0" y="2038.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1009_mpk1_mpk1_csa21" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:SOS*"/> <bbox w="75.0" h="84.0" x="620.5" y="1842.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s35_mpk1_mpk1_sa23"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="633.5" y="1852.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s762_mpk1_mpk1_sa25"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="633.5" y="1877.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1010_mpk1_mpk1_csa111" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GAB1:GRB2 Identifiers_end</body> </html> </notes> <label text="GAB1:GRB2"/> <bbox w="80.0" h="84.0" x="897.0" y="1832.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s967_mpk1_mpk1_sa693"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="916.0" y="1840.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s968_mpk1_mpk1_sa694"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: GRB2-associated binding protein 1 HUGO:GAB1 HGNC:4066 ENTREZ:2549 UNIPROT:Q13480 GENECARDS:GAB1 REACTOME:147726 ATLASONC:GC_GAB1 WIKI:GAB1 GRB2-associated binding protein 2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:11313945 PMID:11940581 References_end</body> </html> </notes> <label text="GAB1"/> <bbox w="50.0" h="25.0" x="916.0" y="1865.5"/> <glyph class="state variable" id="_9f0f0886-9e42-4296-9742-6091ecd466c0"> <state value="" variable="Y977"/> <bbox w="30.0" h="10.0" x="901.3078" y="1860.5"/> </glyph> <glyph class="state variable" id="_6f8e484a-dd6a-4e7f-a380-90f489765ded"> <state value="" variable="Y989"/> <bbox w="30.0" h="10.0" x="951.0" y="1860.6343"/> </glyph> <glyph class="state variable" id="_94a016a3-2efc-4739-b377-2fa9c6ae3bf0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="911.0" y="1873.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1011_mpk1_mpk1_csa14" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:LAMTOR2:MP1* Identifiers_end</body> </html> </notes> <label text="LAMTOR2:MP1*"/> <bbox w="119.0" h="98.0" x="1223.0" y="2254.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s118_mpk1_mpk1_sa73"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="50.0" h="25.0" x="1233.0" y="2264.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s923_mpk1_mpk1_sa74"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="66.0" h="26.0" x="1266.0" y="2284.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1012_mpk1_mpk1_csa15" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:LAMTOR2:MEK*:MP1* Identifiers_end</body> </html> </notes> <label text="LAMTOR2:MEK*:MP1*"/> <bbox w="158.0" h="99.0" x="1207.0" y="2371.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s392_mpk1_mpk1_sa265"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1223.8334" y="2401.1665"/> <glyph class="state variable" id="_2860d97b-a2c6-4c0d-833c-01b30d4c3e5c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1218.8334" y="2412.8328"/> </glyph> <glyph class="state variable" id="_6fc655ea-5710-4125-844d-4cf3348401f1"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1218.8334" y="2404.2925"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s854_mpk1_mpk1_sa615"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="33.0" h="66.0" x="1270.875" y="2380.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s853_mpk1_mpk1_sa616"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="56.125" h="27.5" x="1303.875" y="2399.0"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1013_mpk1_mpk1_csa16" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:LAMTOR2:MEK*:MP1*:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:LAMTOR2:MEK*:MP1*:RAS*:RTK*:SOS*"/> <bbox w="276.0" h="152.0" x="906.0" y="2248.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s123_mpk1_mpk1_sa83"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1079.5" y="2282.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s124_mpk1_mpk1_sa84"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1080.5" y="2307.75"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s128_mpk1_mpk1_sa86"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="64.25" h="23.5" x="1037.75" y="2334.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s126_mpk1_mpk1_sa87"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="50.0" h="25.0" x="995.0" y="2287.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s393_mpk1_mpk1_sa266"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="954.5" y="2330.1665"/> <glyph class="state variable" id="_b8f96bde-a663-4375-8860-977bbaf55444"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="949.5" y="2341.8328"/> </glyph> <glyph class="state variable" id="_79eb56d0-014f-4cf1-be31-88903af728ee"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="949.5" y="2333.2925"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s817_mpk1_mpk1_sa579"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1079.8181" y="2260.4546"/> <glyph class="state variable" id="_ec560b87-bb25-4ef6-9d8c-f3c41a955c1a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1124.8181" y="2273.1323"/> </glyph> <glyph class="state variable" id="_9ef2ad7b-cb09-4e9b-abad-5c6965516ac3"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1124.8181" y="2273.1323"/> </glyph> <glyph class="state variable" id="_e5cf7d46-2d20-4f79-96a8-0f2cde457225"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1124.8181" y="2267.9546"/> </glyph> <glyph class="unit of information" id="_d6ba358f-6aa6-4cd9-aa93-454b36bbd6e3"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1082.3181" y="2255.4546"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s845_mpk1_mpk1_sa605"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1037.125" y="2307.0"/> <glyph class="state variable" id="_dedc3310-3661-43ac-bed6-714b7660f9aa"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1029.625" y="2314.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1014_mpk1_mpk1_csa18" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS*"/> <bbox w="312.0" h="146.0" x="904.5" y="2537.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s160_mpk1_mpk1_sa101"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="969.5" y="2591.5"/> <glyph class="state variable" id="_b0ac8615-9c96-4cf6-9b3e-2eb6bed79906"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="962.0" y="2599.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s396_mpk1_mpk1_sa267"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="970.5" y="2616.8335"/> <glyph class="state variable" id="_c001f9ce-0698-44eb-abc3-2b2e9e9be700"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="963.0" y="2629.1665"/> </glyph> <glyph class="state variable" id="_aff9846e-c6a0-4517-879a-91d3e243a3bd"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="963.0" y="2620.2847"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s846_mpk1_mpk1_sa606"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1095.4432" y="2545.9773"/> <glyph class="state variable" id="_d78f204c-63ea-40bc-a3ab-4defc482eea7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1140.4432" y="2558.655"/> </glyph> <glyph class="state variable" id="_20002ee2-2ddd-4ae9-b279-f7c458a1f221"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1140.4432" y="2558.655"/> </glyph> <glyph class="state variable" id="_c0a5d43b-a167-4e8e-b438-c5d279811394"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1140.4432" y="2553.4773"/> </glyph> <glyph class="unit of information" id="_b8d1baa1-af7e-4335-873d-6aa70158fa15"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1097.9432" y="2540.9773"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s847_mpk1_mpk1_sa607"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1095.125" y="2568.2727"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s848_mpk1_mpk1_sa608"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1096.125" y="2593.2727"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s850_mpk1_mpk1_sa610"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="58.625" h="25.977272" x="1053.375" y="2618.0227"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s851_mpk1_mpk1_sa611"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="66.0" h="26.0" x="1017.0" y="2567.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s849_mpk1_mpk1_sa613"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1055.125" y="2593.0"/> <glyph class="state variable" id="_a324d211-e878-41fa-899b-7d754adbfa15"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1047.625" y="2600.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1015_mpk1_mpk1_csa19" compartmentRef="mpk1_mpk1_c3_mpk1_mpk1_ca3"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS* Identifiers_end</body> </html> </notes> <label text="ERK*:GRB2:LAMTOR2:MEK*:MP1*:RAF1:RAS*:RTK*:SOS*"/> <bbox w="346.0" h="153.0" x="1229.75" y="2532.5"/> <glyph class="macromolecule" id="mpk1_mpk1_s164_mpk1_mpk1_sa103"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 References_end Identifiers_begin: growth factor receptor-bound protein 2 HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="GRB2"/> <bbox w="50.0" h="25.0" x="1436.25" y="2564.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s165_mpk1_mpk1_sa104"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 References_end Identifiers_begin: son of sevenless homolog 1 (Drosophila) GINGF "gingival fibromatosis hereditary 1" HUGO:SOS1 HGNC:11187 ENTREZ:6654 UNIPROT:Q07889 GENECARDS:SOS1 REACTOME:64848 KEGG:6654 ATLASONC:GC_SOS1 WIKI:SOS1 son of sevenless homolog 2 (Drosophila) "son of sevenless (Drosophilia) homolog 2" HUGO:SOS2 HGNC:11188 ENTREZ:6655 UNIPROT:Q07890 GENECARDS:SOS2 REACTOME:64850 ATLASONC:GC_SOS2 WIKI:SOS2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: Sos is recruited from the cytosol to the plasma membrane as a result of its constitutive interaction with Grb2. It is in an autoinhibited state. PMID:17496910 PMID:15574420 PMID:11777939 References_end</body> </html> </notes> <label text="SOS*"/> <bbox w="50.0" h="25.0" x="1436.25" y="2589.25"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s167_mpk1_mpk1_sa106"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 2 "roadblock domain containing 3" ROBLD3 HUGO:LAMTOR2 HGNC:29796 ENTREZ:28956 UNIPROT:Q9Y2Q5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: P14 is an adaptor protein responsible for the recruitment of MP1 to late endosomes. P14 is peripherally associated with the cytoplasmic face of late endosomes. PMID:17178906 PMID:12479806 References_end</body> </html> </notes> <label text="LAMTOR2"/> <bbox w="65.5" h="29.0" x="1388.5" y="2615.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s168_mpk1_mpk1_sa107"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: late endosomal/lysosomal adaptor MODULE:MAPK and MTOR activator 3 MAP2K1IP1 "MODULE:MAPK scaffold protein 1" MAPKSP1 "mitogen-activated protein kinase kinase 1 interacting protein 1" HUGO:LAMTOR3 HGNC:15606 ENTREZ:8649 UNIPROT:Q9UHA4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MP1 is localised in late endosomes by P14 forming a very stable heterodimeric complex that is required for ERK activation. It is required for efficient and sustained EGF-induced MEK and ERK activation (in late endosomes) PMID:17178906 References_end</body> </html> </notes> <label text="MP1*"/> <bbox w="66.0" h="26.0" x="1357.0" y="2557.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s170_mpk1_mpk1_sa109"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="66.0" h="26.0" x="1305.75" y="2587.5"/> <glyph class="state variable" id="_b865870b-b3a5-4937-8d17-e5f254321b74"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1298.25" y="2595.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s385_mpk1_mpk1_sa258"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="66.0" h="26.0" x="1307.1666" y="2639.1665"/> <glyph class="state variable" id="_7ea11688-b7c4-4931-b724-5b8c4b660d12"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.6666" y="2651.6975"/> </glyph> <glyph class="state variable" id="_afd92290-7e5c-48f7-ae72-3de8957947fa"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.6666" y="2642.0186"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s399_mpk1_mpk1_sa268"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="1306.5" y="2613.1665"/> <glyph class="state variable" id="_7bc84657-eec5-4665-8772-307269305532"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.0" y="2625.4995"/> </glyph> <glyph class="state variable" id="_dcbd7163-732a-4070-b756-060e1ae70dd5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1299.0" y="2616.6177"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s819_mpk1_mpk1_sa581"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 References_end Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> Identifiers_begin: epidermal growth factor receptor "epidermal growth factor receptor (avian erythroblastic leukemia viral (v-erb-b) oncogene homolog)" ERBB HUGO:EGFR HGNC:3236 ENTREZ:1956 UNIPROT:P00533 GENECARDS:EGFR REACTOME:54208 KEGG:1956 ATLASONC:GC_EGFR WIKI:EGFR v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 neuro/glioblastoma derived oncogene homolog (avian) NGL "v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)" HUGO:ERBB2 HGNC:3430 ENTREZ:2064 UNIPROT:P04626 GENECARDS:ERBB2 REACTOME:54422 KEGG:2064 ATLASONC:ERBB2ID162ch17q11 WIKI:ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) LCCS2 "lethal congenital contracture syndrome 2" HUGO:ERBB3 HGNC:3431 ENTREZ:2065 UNIPROT:P21860 GENECARDS:ERBB3 REACTOME:403310 KEGG:2065 ATLASONC:ERBB3ID40479ch12q13 WIKI:ERBB3 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) "v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4" HUGO:ERBB4 HGNC:3432 ENTREZ:2066 UNIPROT:Q15303 GENECARDS:ERBB4 REACTOME:54426 KEGG:2066 ATLASONC:GC_ERBB4 WIKI:ERBB4 fibroblast growth factor receptor 1 FLT2 "fms-related tyrosine kinase 2" KAL2 HUGO:FGFR1 HGNC:3688 ENTREZ:2260 UNIPROT:P11362 GENECARDS:FGFR1 REACTOME:402793 KEGG:2260 ATLASONC:FGFR1113 WIKI:FGFR1 fibroblast growth factor receptor 2 "bacteria-expressed kinase" BEK CFD1 "craniofacial dysostosis 1" "Jackson-Weiss syndrome" JWS "keratinocyte growth factor receptor" KGFR HUGO:FGFR2 HGNC:3689 ENTREZ:2263 UNIPROT:P21802 GENECARDS:FGFR2 REACTOME:403305 KEGG:2263 ATLASONC:FGFR2ID40570ch10q26 WIKI:FGFR2 fibroblast growth factor receptor 3 ACH "achondroplasia thanatophoric dwarfism" HUGO:FGFR3 HGNC:3690 ENTREZ:2261 UNIPROT:P22607 GENECARDS:FGFR3 REACTOME:403340 KEGG:2261 ATLASONC:FGFR99 WIKI:FGFR3 fibroblast growth factor receptor 4 HUGO:FGFR4 HGNC:3691 ENTREZ:2264 UNIPROT:P22455 GENECARDS:FGFR4 REACTOME:54820 KEGG:2264 ATLASONC:FGFR4ID512ch5q35 WIKI:FGFR4 fms-related tyrosine kinase 1 FLT "fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)" HUGO:FLT1 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 GENECARDS:FLT1 REACTOME:403120 KEGG:2321 ATLASONC:GC_FLT1 WIKI:FLT1 fms-related tyrosine kinase 3 HUGO:FLT3 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 GENECARDS:FLT3 KEGG:2322 ATLASONC:FLT3ID144 WIKI:FLT3 fms-related tyrosine kinase 4 HUGO:FLT4 HGNC:3767 ENTREZ:2324 UNIPROT:P35916 GENECARDS:FLT4 REACTOME:67176 KEGG:2324 ATLASONC:GC_FLT4 WIKI:FLT4 platelet-derived growth factor receptor alpha polypeptide HUGO:PDGFRA HGNC:8803 ENTREZ:5156 UNIPROT:P16234 GENECARDS:PDGFRA REACTOME:61602 KEGG:5156 ATLASONC:GC_PDGFRA WIKI:PDGFRA platelet-derived growth factor receptor beta polypeptide PDGFR HUGO:PDGFRB HGNC:8804 ENTREZ:5159 UNIPROT:P09619 GENECARDS:PDGFRB REACTOME:61600 KEGG:5159 ATLASONC:PDGFRBID21ch5q32 WIKI:PDGFRB A generic name for this family of receptors that contain a tyrosine kinase activity. rhotekin HUGO:RTKN HGNC:10466 ENTREZ:6242 UNIPROT:Q9BST9 GENECARDS:RTKN ATLASONC:GC_RTKN WIKI:RTKN Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RTKs exist as inactive monomers; after binding to their ligands they form dimers and their intracellular domains are activated. PMID:17496910 PMID:12040186 PMID:19568798 PMID:14585353 RTK stands for receptor tyrosine kinase and consists of approx. 20 different classes (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase) References_end</body> </html> </notes> <label text="RTK*"/> <bbox w="50.0" h="25.0" x="1437.8182" y="2541.0908"/> <glyph class="state variable" id="_874a35e0-26f6-46ac-beac-876ba0f6ee1d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1482.8182" y="2553.7686"/> </glyph> <glyph class="state variable" id="_3759715c-d311-4f0c-bb7f-514c500384bb"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1482.8182" y="2553.7686"/> </glyph> <glyph class="state variable" id="_9ba52174-529b-44fb-a4d5-670d4b92df51"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1482.8182" y="2548.5908"/> </glyph> <glyph class="unit of information" id="_3c843093-fbfe-4b96-9f9b-b09d8069efa4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1440.3182" y="2536.0908"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s852_mpk1_mpk1_sa614"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> Identifiers_begin: RAS p21 protein activator (GTPase activating protein) 1 HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1 RAS p21 protein activator 2 HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2 RAS p21 protein activator 3 HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3 RAS p21 protein activator 4 HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4 v-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS1 HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog" HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS neuroblastoma RAS viral (v-ras) oncogene homolog HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR Maps_Modules_end References_begin: PMID:21102635 RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output. RasGRP1 activates Golgi-associated Ras on this compartment. K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus. Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle. H-Ras but not K-Ras signalling was dependent on endocytosis. PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955 References_end</body> </html> </notes> <label text="RAS*"/> <bbox w="50.0" h="25.0" x="1387.875" y="2590.0"/> <glyph class="state variable" id="_6082744e-d388-4b9b-92a6-85bfd18195e2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1380.375" y="2597.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1016_mpk1_mpk1_csa71" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:GSK3_beta_*:RSK* Identifiers_end</body> </html> </notes> <label text="ERK*:GSK3β*:RSK*"/> <bbox w="111.0" h="106.0" x="1659.0" y="2631.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s763_mpk1_mpk1_sa352"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="1691.0" y="2637.4614"/> <glyph class="state variable" id="_505c64e5-5beb-4289-9591-334ecfa85dcb"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1683.5" y="2649.318"/> </glyph> <glyph class="state variable" id="_e465cdf6-7369-4c19-aa0d-f2b118edd04f"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1683.5" y="2640.0115"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s591_mpk1_mpk1_sa353"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 GENECARDS:GSK3B REACTOME:404223 ATLASONC:GSK3BID40761ch3q13 WIKI:GSK3B Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:cellcycle / MODULE:CYCLIND MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:12615961 PMID:20537194 glycogen synthase kinase 3 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end</body> </html> Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 GENECARDS:GSK3B REACTOME:404223 ATLASONC:GSK3BID40761ch3q13 WIKI:GSK3B Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:cellcycle / MODULE:CYCLIND MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:12615961 PMID:20537194 glycogen synthase kinase 3 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end</body> </html> Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B HGNC:4617 ENTREZ:2932 UNIPROT:P49841 GENECARDS:GSK3B REACTOME:404223 ATLASONC:GSK3BID40761ch3q13 WIKI:GSK3B Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:cellcycle / MODULE:CYCLIND MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:12615961 PMID:20537194 glycogen synthase kinase 3 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. PMID:16039586 References_end</body> </html> </notes> <label text="GSK3β*"/> <bbox w="63.0" h="27.0" x="1684.0" y="2663.4614"/> <glyph class="state variable" id="_f27163c0-ae57-44a5-a1d5-78586717c9b5"> <state value="" variable="S9"/> <bbox w="20.0" h="10.0" x="1674.3878" y="2658.4614"/> </glyph> <glyph class="state variable" id="_af273a5c-36c9-412b-a46b-2e827698d172"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1676.5" y="2671.9614"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s592_mpk1_mpk1_sa354"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - we group here all isoforms of RSK family, as we do not have enough information about the differencies in their behaviour ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: ribosomal protein S6 kinase 90kDa polypeptide 1 "ribosomal protein S6 kinase 90kD polypeptide 1" HUGO:RPS6KA1 HGNC:10430 ENTREZ:6195 UNIPROT:Q15418 ribosomal protein S6 kinase 90kDa polypeptide 2 "ribosomal protein S6 kinase 90kD polypeptide 2" HUGO:RPS6KA2 HGNC:10431 ENTREZ:6196 UNIPROT:Q15349 ribosomal protein S6 kinase 90kDa polypeptide 3 CLS "Coffin-Lowry syndrome" "mental retardation X-linked 19" MRX19 "ribosomal protein S6 kinase 90kD polypeptide 3" HUGO:RPS6KA3 HGNC:10432 ENTREZ:6197 UNIPROT:P51812 ribosomal protein S6 kinase 90kDa polypeptide 6 "ribosomal protein S6 kinase 90kD polypeptide 6" HUGO:RPS6KA6 HGNC:10435 ENTREZ:27330 UNIPROT:Q9UK32 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: RSK2 is a well known ERK substrate in the cytoplasm. RSKs are exclusively activated by ERK. Activated RSK can be found in both nuclear and cytoplasmic compartments. PMID:15239952 PMID:15187187 References_end Identifiers_begin: ribosomal protein S6 kinase 90kDa polypeptide 1 "ribosomal protein S6 kinase 90kD polypeptide 1" HUGO:RPS6KA1 HGNC:10430 ENTREZ:6195 UNIPROT:Q15418 GENECARDS:RPS6KA1 REACTOME:57795 KEGG:6195 ATLASONC:RPS6KA1ID43477ch1p36 WIKI:RPS6KA1 ribosomal protein S6 kinase 90kDa polypeptide 2 "ribosomal protein S6 kinase 90kD polypeptide 2" HUGO:RPS6KA2 HGNC:10431 ENTREZ:6196 UNIPROT:Q15349 GENECARDS:RPS6KA2 REACTOME:57797 KEGG:6196 ATLASONC:GC_RPS6KA2 WIKI:RPS6KA2 ribosomal protein S6 kinase 90kDa polypeptide 3 CLS "Coffin-Lowry syndrome" "mental retardation X-linked 19" MRX19 "ribosomal protein S6 kinase 90kD polypeptide 3" HUGO:RPS6KA3 HGNC:10432 ENTREZ:6197 UNIPROT:P51812 GENECARDS:RPS6KA3 REACTOME:57799 KEGG:6197 ATLASONC:GC_RPS6KA3 WIKI:RPS6KA3 ribosomal protein S6 kinase 90kDa polypeptide 6 "ribosomal protein S6 kinase 90kD polypeptide 6" HUGO:RPS6KA6 HGNC:10435 ENTREZ:27330 UNIPROT:Q9UK32 GENECARDS:RPS6KA6 REACTOME:57801 KEGG:27330 ATLASONC:GC_RPS6KA6 WIKI:RPS6KA6 ribosomal protein S6 kinase 90kDa polypeptide 4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:PIM1 HGNC:8986 ENTREZ:5292 UNIPROT:P11309 GENECARDS:PIM1 KEGG:9361 ATLASONC:PIM1ID261 WIKI:PIM1 ribosomal protein S6 kinase, 90kDa, polypeptide 5 HUGO:RPS6KA5 HGNC:10434 ENTREZ:9252 UNIPROT:O75582 GENECARDS:RPS6KA5 REACTOME:93593 KEGG:9252 ATLASONC:GC_RPS6KA5 WIKI:RPS6KA5 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RSK2 is a well known ERK substrate in the cytoplasm. RSKs are exclusively activated by ERK. Activated RSK can be found in both nuclear and cytoplasmic compartments. PMID:15239952 PMID:15187187 PMID:16286006 PMID:21233202 References_end Identifiers_begin: ribosomal protein S6 kinase 90kDa polypeptide 1 "ribosomal protein S6 kinase 90kD polypeptide 1" HUGO:RPS6KA1 HGNC:10430 ENTREZ:6195 UNIPROT:Q15418 GENECARDS:RPS6KA1 REACTOME:57795 KEGG:6195 ATLASONC:RPS6KA1ID43477ch1p36 WIKI:RPS6KA1 ribosomal protein S6 kinase 90kDa polypeptide 2 "ribosomal protein S6 kinase 90kD polypeptide 2" HUGO:RPS6KA2 HGNC:10431 ENTREZ:6196 UNIPROT:Q15349 GENECARDS:RPS6KA2 REACTOME:57797 KEGG:6196 ATLASONC:GC_RPS6KA2 WIKI:RPS6KA2 ribosomal protein S6 kinase 90kDa polypeptide 3 CLS "Coffin-Lowry syndrome" "mental retardation X-linked 19" MRX19 "ribosomal protein S6 kinase 90kD polypeptide 3" HUGO:RPS6KA3 HGNC:10432 ENTREZ:6197 UNIPROT:P51812 GENECARDS:RPS6KA3 REACTOME:57799 KEGG:6197 ATLASONC:GC_RPS6KA3 WIKI:RPS6KA3 ribosomal protein S6 kinase 90kDa polypeptide 6 "ribosomal protein S6 kinase 90kD polypeptide 6" HUGO:RPS6KA6 HGNC:10435 ENTREZ:27330 UNIPROT:Q9UK32 GENECARDS:RPS6KA6 REACTOME:57801 KEGG:27330 ATLASONC:GC_RPS6KA6 WIKI:RPS6KA6 ribosomal protein S6 kinase 90kDa polypeptide 4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:RPS6KA4 HGNC:10433 ENTREZ:8986 UNIPROT:O75676 GENECARDS:RPS6KA4 REACTOME:93591 KEGG:8986 ATLASONC:GC_RPS6KA4 WIKI:RPS6KA4 HUGO:PIM1 HGNC:8986 ENTREZ:5292 UNIPROT:P11309 GENECARDS:PIM1 KEGG:9361 ATLASONC:PIM1ID261 WIKI:PIM1 ribosomal protein S6 kinase, 90kDa, polypeptide 5 HUGO:RPS6KA5 HGNC:10434 ENTREZ:9252 UNIPROT:O75582 GENECARDS:RPS6KA5 REACTOME:93593 KEGG:9252 ATLASONC:GC_RPS6KA5 WIKI:RPS6KA5 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:PI3K_AKT_MTOR MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: RSK2 is a well known ERK substrate in the cytoplasm. RSKs are exclusively activated by ERK. Activated RSK can be found in both nuclear and cytoplasmic compartments. PMID:15239952 PMID:15187187 PMID:16286006 PMID:21233202 References_end</body> </html> </notes> <label text="RSK*"/> <bbox w="50.0" h="25.0" x="1689.0" y="2689.4614"/> <glyph class="state variable" id="_4c94aa3a-a6f4-41df-9e97-deb54deff641"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1681.5" y="2696.9614"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1017_mpk1_mpk1_csa49" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP6:ERK* Identifiers_end</body> </html> </notes> <label text="DUSP6:ERK*"/> <bbox w="90.0" h="83.0" x="2093.0" y="2462.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s374_mpk1_mpk1_sa249"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 6 HUGO:DUSP6 HGNC:3072 ENTREZ:1848 UNIPROT:Q16828 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: DUSP6 may capture activated ERK2 dephosphorylate it and anchor the inactive kinase in the cytoplasm. PMID:17052211 References_end</body> </html> </notes> <label text="DUSP6"/> <bbox w="50.0" h="25.0" x="2107.5" y="2470.0"/> <glyph class="state variable" id="_f3462dee-695b-4d5d-8025-de32e9d1775f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2102.5" y="2477.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s373_mpk1_mpk1_sa250"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2115.5" y="2496.0"/> <glyph class="state variable" id="_a7432642-ca4a-4776-b66d-d2008e3c68e7"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2110.5" y="2507.8567"/> </glyph> <glyph class="state variable" id="_7856273d-2743-4704-a655-2d31999bf830"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2110.5" y="2498.55"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1018_mpk1_mpk1_csa44" compartmentRef="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:GPCR*:GRK*:MEK*:RAF1:_beta_-Arrestin2* Identifiers_end</body> </html> </notes> <label text="ERK*:GPCR*:GRK*:MEK*:RAF1:β-Arrestin2*"/> <bbox w="234.0" h="160.0" x="2468.0" y="2080.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s350_mpk1_mpk1_sa228"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: arrestin beta 2 ARR2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> Identifiers_begin: Arrestin beta 1 HUGO:ARRB1 HGNC:711 ENTREZ:408 UNIPROT:P49407 GENECARDS:ARRB1 REACTOME:404181 KEGG:408 ATLASONC:GC_ARRB1 WIKI:ARRB1 Arrestin beta 2 HUGO:ARRB2 HGNC:712 ENTREZ:409 UNIPROT:P32121 GENECARDS:ARRB2 REACTOME:50317 KEGG:409 ATLASONC:GC_ARRB2 WIKI:ARRB2 ARR2 arrestin 3", BARR2, DKFZp686L0365 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19853559 PMID:18497258 PMID:15618519 Beta-ARRESTIN 2 bind to both GRK-phosphorylated receptor and to the component kinases of the ERK cascade resulting in assembly of an ERK activation complex that is targeted into endosomal vesicles. MEK1/2 and ERK1/2 were reported to be localised in early endosomes to which they are recruited mainly by beta-ARRESTIN. PMID:11226259 PMID:19565474 References_end</body> </html> </notes> <label text="β-Arrestin2*"/> <bbox w="49.0" h="77.0" x="2600.0" y="2137.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s351_mpk1_mpk1_sa229"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end Identifiers_begin: v-raf-1 murine leukemia viral oncogene homolog 1 HUGO:RAF1 HGNC:9829 ENTREZ:5894 UNIPROT:P04049 GENECARDS:RAF1 REACTOME:58255 KEGG:5894 ATLASONC:RAF1ID42032ch3p25 WIKI:RAF1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Active KRas (on late endosomes) recruits Raf1 (C-Raf) to elicit a MODULE:MAPK signalling pathway. Raf1 MEK1/2 and ERK1/2 may act in the outer side of the Golgi apparatus and attenuate proliferation. PMID:19289794 PMID:19565474 References_end</body> </html> </notes> <label text="RAF1"/> <bbox w="50.0" h="25.0" x="2537.0" y="2139.0"/> <glyph class="state variable" id="_f2ad30b3-1fd1-4905-bdfc-47f03c2f1263"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2529.5" y="2146.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s352_mpk1_mpk1_sa230"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="2550.7273" y="2188.5908"/> <glyph class="state variable" id="_dcf2e27a-9238-4e1c-852a-0c44c0562515"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2543.2273" y="2200.4475"/> </glyph> <glyph class="state variable" id="_02400c85-64c9-4d74-bb0a-3fa1a2534691"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2543.2273" y="2191.1409"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s353_mpk1_mpk1_sa231"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2549.0" y="2164.4092"/> <glyph class="state variable" id="_00378b10-eb85-4479-96ff-bbbdc8320d55"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2541.5" y="2176.0754"/> </glyph> <glyph class="state variable" id="_0f22942c-a9f5-491b-bf62-7eee03a76b36"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2541.5" y="2167.5352"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s540_mpk1_mpk1_sa314"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2599.5" y="2111.3333"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s816_mpk1_mpk1_sa578"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="50.0" h="25.0" x="2601.5454" y="2088.9092"/> <glyph class="state variable" id="_3c359c73-8bb0-40b0-af54-e5efe1b51c36"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2596.5454" y="2096.4092"/> </glyph> <glyph class="unit of information" id="_075ce3f9-4e3a-49b8-adc0-4809e54d636b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2604.0454" y="2083.9092"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1019_mpk1_mpk1_csa70" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:LEF_TCF*:_beta_-Catenin* Identifiers_end</body> </html> </notes> <label text="LEF_TCF*:β-Catenin*"/> <bbox w="120.0" h="83.0" x="327.0" y="3024.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s765_mpk1_mpk1_sa350"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body> <html> <body>Identifiers_begin: catenin (cadherin-associated protein) beta 1 88kDa "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 References_end Identifiers_begin: Catenin (cadherin-associated protein) beta 1 88 kDa HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 GENECARDS:CTNNB1 REACTOME:53048 KEGG:1499 ATLASONC:CTNNB1ID71 WIKI:CTNNB1 "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB catenin (cadherin-associated protein) beta 1 armadillo, beta-catenin Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19619488 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 PMID:17143292 PMID:23343194 References_end</body> </html> Identifiers_begin: Catenin (cadherin-associated protein) beta 1 88 kDa HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 GENECARDS:CTNNB1 REACTOME:53048 KEGG:1499 ATLASONC:CTNNB1ID71 WIKI:CTNNB1 "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB catenin (cadherin-associated protein) beta 1 armadillo, beta-catenin Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19619488 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 PMID:17143292 PMID:23343194 References_end</body> </html> Identifiers_begin: Catenin (cadherin-associated protein) beta 1 88 kDa HUGO:CTNNB1 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 GENECARDS:CTNNB1 REACTOME:53048 KEGG:1499 ATLASONC:CTNNB1ID71 WIKI:CTNNB1 "catenin (cadherin-associated protein) beta 1 (88kD)" CTNNB catenin (cadherin-associated protein) beta 1 armadillo, beta-catenin Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:CELL_CELL_ADHESIONS MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: PMID:19619488 ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex. Once GSK3B is inactivated beta-catenin (CTNNB1) is stabilised in the cytoplasm and translocate to the nucleus and then interacts with TCF/LEF and upregulates its downstream targets such as cyclin D1 and c-myc (not modelled). PMID:16039586 PMID:16039586 PMID:17143292 PMID:23343194 References_end</body> </html> </notes> <label text="β-Catenin*"/> <bbox w="72.0" h="26.0" x="351.6154" y="3035.2307"/> <glyph class="state variable" id="_d7137bf5-7489-408d-8b56-e48a1cfb793a"> <state value="" variable="S45"/> <bbox w="25.0" h="10.0" x="375.0294" y="3056.2307"/> </glyph> <glyph class="state variable" id="_a90e2c73-7a41-416d-b3a5-75ac9ed1fddc"> <state value="" variable="T41"/> <bbox w="25.0" h="10.0" x="410.559" y="3056.2307"/> </glyph> <glyph class="state variable" id="_96fb8abe-9b06-4850-b000-c9faad4b8af5"> <state value="" variable="S37"/> <bbox w="25.0" h="10.0" x="411.1154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_0e419f8f-344b-420e-8abc-c99f6b1614a1"> <state value="" variable="S33"/> <bbox w="25.0" h="10.0" x="375.14404" y="3030.2307"/> </glyph> <glyph class="state variable" id="_7e1d3e9c-457f-43e1-b0b7-29aaaa636b26"> <state value="" variable="K19"/> <bbox w="25.0" h="10.0" x="339.55865" y="3030.2307"/> </glyph> <glyph class="state variable" id="_85ce044f-b029-4119-b287-f074bca53d67"> <state value="" variable="K49"/> <bbox w="25.0" h="10.0" x="339.1154" y="3056.0503"/> </glyph> <glyph class="state variable" id="_1e0a5f30-ce05-4d78-87a2-abab3119686f"> <state value="" variable="Y142"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_aecb6839-ec1b-41db-9e60-cc76ab4b3d0e"> <state value="" variable="S552"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_a7687334-a049-4bc3-af3a-5fe0354d6977"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="346.6154" y="3043.2307"/> </glyph> <glyph class="state variable" id="_3a577fc6-10f2-46b3-8f9e-9e53c2809076"> <state value="" variable="K394"/> <bbox w="30.0" h="10.0" x="337.05865" y="3030.2307"/> </glyph> <glyph class="state variable" id="_652e5b54-48b7-4fe8-93f1-bd5cb972c09c"> <state value="" variable="Y654"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_ec69efeb-3d4e-4162-b74d-c43684484fa6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="346.6154" y="3037.846"/> </glyph> <glyph class="state variable" id="_4871881f-8424-46ac-9aa1-3ddb1ab73fa9"> <state value="" variable="S522"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> <glyph class="state variable" id="_d410f72f-2a73-43a4-874c-e1375b557df9"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="346.6154" y="3043.2307"/> </glyph> <glyph class="state variable" id="_a68ca309-8e5d-4724-b1a6-cd92ea5a4725"> <state value="" variable="S675"/> <bbox w="30.0" h="10.0" x="408.059" y="3056.2307"/> </glyph> <glyph class="state variable" id="_c07cbd85-5352-44fb-9655-d6954d1ed2aa"> <state value="" variable="K345"/> <bbox w="30.0" h="10.0" x="408.6154" y="3030.3704"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s766_mpk1_mpk1_sa351"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: lymphoid enhancer-binding factor 1 HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 transcription factor 7 (T-cell specific HMG-box) HUGO:TCF7 HGNC:11639 ENTREZ:6932 UNIPROT:P36402 transcription factor 7-like 1 (T-cell specific HMG-box) TCF3 HUGO:TCF7L1 HGNC:11640 ENTREZ:83439 UNIPROT:Q9HCS4 transcription factor 7-like 2 (T-cell specific HMG-box) TCF4 HUGO:TCF7L2 HGNC:11641 ENTREZ:6934 UNIPROT:Q9NQB0 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1) HUGO:PCBD2 HGNC:24474 ENTREZ:84105 UNIPROT:Q9H0N5 GENECARDS:PCBD2 KEGG:84105 WIKI:PCBD2 HNF1 homeobox A MODY3 TCF1 "transcription factor 1 hepatic; LF-B1 hepatic nuclear factor (HNF1) albumin proximal factor" HUGO:HNF1A HGNC:11621 ENTREZ:6927 UNIPROT:P20823 GENECARDS:HNF1A REACTOME:403244 KEGG:6927 ATLASONC:GC_HNF1A WIKI:HNF1A HNF1 homeobox B TCF2 "transcription factor 2 hepatic; LF-B3; variant hepatic nuclear factor" HUGO:HNF1B HGNC:11630 ENTREZ:6928 UNIPROT:P35680 GENECARDS:HNF1B REACTOME:403844 KEGG:6928 ATLASONC:GC_HNF1B WIKI:HNF1B transcription factor 3 HUGO:TCF3 HGNC:11633 ENTREZ:6929 UNIPROT:P15923 GENECARDS:TCF3 REACTOME:65901 KEGG:6929 ATLASONC:E2A WIKI:TCF3 transcription factor 4 HUGO:TCF4 HGNC:11634 ENTREZ:6925 UNIPROT:P15884 GENECARDS:TCF4 REACTOME:57613 KEGG:6925 ATLASONC:GC_TCF4 WIKI:TCF4 CCAAT/enhancer binding protein (C/EBP) beta TCF5 HUGO:CEBPB HGNC:1834 ENTREZ:1051 UNIPROT:P17676 GENECARDS:CEBPB REACTOME:51866 KEGG:1051 ATLASONC:GC_CEBPB WIKI:CEBPB transcription factor-like 5 (basic helix-loop-helix) HUGO:TCFL5 HGNC:11646 ENTREZ:10732 UNIPROT:Q9UL49 GENECARDS:TCFL5 KEGG:10732 WIKI:TCFL5 info transcription factor A mitochondrial HUGO:TFAM HGNC:11741 ENTREZ:7019 UNIPROT:Q00059 GENECARDS:TFAM REACTOME:65899 KEGG:7019 ATLASONC:GC_TFAM WIKI:TFAM transcription factor 7 (T-cell specific HMG-box) HUGO:TCF7 HGNC:11639 ENTREZ:6932 UNIPROT:P36402 GENECARDS:TCF7 KEGG:6932 ATLASONC:GC_TCF7 WIKI:TCF7 transcription factor 7-like 1 (T-cell specific HMG-box) HUGO:TCF7L1 HGNC:11640 ENTREZ:83439 UNIPROT:Q9HCS4 GENECARDS:TCF7L1 KEGG:83439 ATLASONC:GC_TCF7L1 WIKI:TCF7L1 transcription factor 7-like 2 (T-cell specific HMG-box) HUGO:TCF7L2 HGNC:11641 ENTREZ:6934 UNIPROT:Q9NQB0 GENECARDS:TCF7L2 REACTOME:65596 KEGG:6934 ATLASONC:GC_TCF7L2 WIKI:TCF7L2 zinc finger E-box binding homeobox 1 TCF8 HUGO:ZEB1 HGNC:11642 ENTREZ:6935 UNIPROT:P37275 GENECARDS:ZEB1 KEGG:6935 ATLASONC:GC_ZEB1 WIKI:ZEB1 GC-rich sequence DNA-binding factor 2 PREVIOUS SYMBOLS/ C2orf3 "chromosome 2 open reading frame 3" TCF9 "transcription factor 9 (binds GC-rich sequences)" HUGO:GCFC2 HGNC:1317 ENTREZ:6936 UNIPROT:P16383 GENECARDS:GCFC2 KEGG:6936 WIKI:GCFC2 lymphoid enhancer-binding factor 1 HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 GENECARDS:LEF1 KEGG:51176 ATLASONC:GC_LEF1 WIKI:LEF1 nuclear factor (erythroid-derived 2)-like 1 TCF11 HUGO:NFE2L1 HGNC:7781 ENTREZ:4779 UNIPROT:Q14494 GENECARDS:NFE2L1 KEGG:4779 ATLASONC:GC_NFE2L1 WIKI:NFE2L1 transcription factor 12 HUGO:TCF12 HGNC:11623 ENTREZ:6938 UNIPROT:Q99081 GENECARDS:TCF12 REACTOME:56728 KEGG:6938 ATLASONC:TCF12ID406 WIKI:TCF12 TEA domain family member 1 (SV40 transcriptional enhancer factor) AA "atrophia areata peripapillary chorioretinal degeneration" TCF13 HUGO:TEAD1 HGNC:11714 ENTREZ:7003 UNIPROT:P28347 GENECARDS:TEAD1 REACTOME:65831 KEGG:7003 ATLASONC:GC_TEAD1 WIKI:TEAD1 TEA domain family member 4 TCF13L1 HUGO:TEAD4 HGNC:11717 ENTREZ:7004 UNIPROT:Q15561 GENECARDS:TEAD4 REACTOME:65837 KEGG:7004 WIKI:TEAD4 hepatocyte nuclear factor 4 alpha MODY MODY1 TCF14 HUGO:HNF4A HGNC:5024 ENTREZ:3172 UNIPROT:P41235 GENECARDS:HNF4A REACTOME:211473 KEGG:3172 ATLASONC:GC_HNF4A WIKI:HNF4A transcription factor 15 (basic helix-loop-helix) HUGO:TCF15 HGNC:11627 ENTREZ:6939 UNIPROT:Q12870 GENECARDS:TCF15 KEGG:6939 ATLASONC:GC_TCF15 WIKI:TCF15 conserved helix-loop-helix ubiquitous kinase TCF16 HUGO:CHUK HGNC:1974 ENTREZ:1147 UNIPROT:O15111 GENECARDS:CHUK REACTOME:57214 KEGG:1147 ATLASONC:GC_CHUK WIKI:CHUK zinc finger protein 354A TCF17 HUGO:ZNF354A HGNC:11628 ENTREZ:6940 UNIPROT:O60765 GENECARDS:ZNF354A REACTOME:65741 KEGG:6940 WIKI:ZNF354A transcription factor 19 HUGO:TCF19 HGNC:11629 ENTREZ:6941 UNIPROT:Q9Y242 GENECARDS:TCF19 KEGG:6941 WIKI:TCF19 transcription factor 20 HUGO:TCF20 HGNC:11631 ENTREZ:6942 UNIPROT:Q9UGU0 GENECARDS:TCF20 KEGG:6942 WIKI:TCF20 transcription factor 21 HUGO:TCF21 HGNC:11632 ENTREZ:6943 UNIPROT:O43680 GENECARDS:TCF21 KEGG:6943 ATLASONC:GC_TCF21 WIKI:TCF21 transcription factor 23 HUGO:TCF23 HGNC:18602 ENTREZ:150921 UNIPROT:Q7RTU1 GENECARDS:TCF23 KEGG:150921 WIKI:TCF23 transcription factor 24 HUGO:TCF24 HGNC:32275 ENTREZ:100129654 UNIPROT:Q7RTU0 GENECARDS:TCF24 KEGG:100129654 WIKI:TCF24 transcription factor 25 HUGO:TCF25 HGNC:29181 ENTREZ:22980 UNIPROT:Q9BQ70 GENECARDS:TCF25 KEGG:22980 ATLASONC:GC_TCF25 WIKI:TCF25 TCF3 TCF4 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:19623618 PMID:19619488 HNF1 homeobox Phosphorylation sites specific for HIPK2 not known PMID:21285352 References_end</body> </html> Identifiers_begin: pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1) HUGO:PCBD2 HGNC:24474 ENTREZ:84105 UNIPROT:Q9H0N5 GENECARDS:PCBD2 KEGG:84105 WIKI:PCBD2 HNF1 homeobox A MODY3 TCF1 "transcription factor 1 hepatic; LF-B1 hepatic nuclear factor (HNF1) albumin proximal factor" HUGO:HNF1A HGNC:11621 ENTREZ:6927 UNIPROT:P20823 GENECARDS:HNF1A REACTOME:403244 KEGG:6927 ATLASONC:GC_HNF1A WIKI:HNF1A HNF1 homeobox B TCF2 "transcription factor 2 hepatic; LF-B3; variant hepatic nuclear factor" HUGO:HNF1B HGNC:11630 ENTREZ:6928 UNIPROT:P35680 GENECARDS:HNF1B REACTOME:403844 KEGG:6928 ATLASONC:GC_HNF1B WIKI:HNF1B transcription factor 3 HUGO:TCF3 HGNC:11633 ENTREZ:6929 UNIPROT:P15923 GENECARDS:TCF3 REACTOME:65901 KEGG:6929 ATLASONC:E2A WIKI:TCF3 transcription factor 4 HUGO:TCF4 HGNC:11634 ENTREZ:6925 UNIPROT:P15884 GENECARDS:TCF4 REACTOME:57613 KEGG:6925 ATLASONC:GC_TCF4 WIKI:TCF4 CCAAT/enhancer binding protein (C/EBP) beta TCF5 HUGO:CEBPB HGNC:1834 ENTREZ:1051 UNIPROT:P17676 GENECARDS:CEBPB REACTOME:51866 KEGG:1051 ATLASONC:GC_CEBPB WIKI:CEBPB transcription factor-like 5 (basic helix-loop-helix) HUGO:TCFL5 HGNC:11646 ENTREZ:10732 UNIPROT:Q9UL49 GENECARDS:TCFL5 KEGG:10732 WIKI:TCFL5 info transcription factor A mitochondrial HUGO:TFAM HGNC:11741 ENTREZ:7019 UNIPROT:Q00059 GENECARDS:TFAM REACTOME:65899 KEGG:7019 ATLASONC:GC_TFAM WIKI:TFAM transcription factor 7 (T-cell specific HMG-box) HUGO:TCF7 HGNC:11639 ENTREZ:6932 UNIPROT:P36402 GENECARDS:TCF7 KEGG:6932 ATLASONC:GC_TCF7 WIKI:TCF7 transcription factor 7-like 1 (T-cell specific HMG-box) HUGO:TCF7L1 HGNC:11640 ENTREZ:83439 UNIPROT:Q9HCS4 GENECARDS:TCF7L1 KEGG:83439 ATLASONC:GC_TCF7L1 WIKI:TCF7L1 transcription factor 7-like 2 (T-cell specific HMG-box) HUGO:TCF7L2 HGNC:11641 ENTREZ:6934 UNIPROT:Q9NQB0 GENECARDS:TCF7L2 REACTOME:65596 KEGG:6934 ATLASONC:GC_TCF7L2 WIKI:TCF7L2 zinc finger E-box binding homeobox 1 TCF8 HUGO:ZEB1 HGNC:11642 ENTREZ:6935 UNIPROT:P37275 GENECARDS:ZEB1 KEGG:6935 ATLASONC:GC_ZEB1 WIKI:ZEB1 GC-rich sequence DNA-binding factor 2 PREVIOUS SYMBOLS/ C2orf3 "chromosome 2 open reading frame 3" TCF9 "transcription factor 9 (binds GC-rich sequences)" HUGO:GCFC2 HGNC:1317 ENTREZ:6936 UNIPROT:P16383 GENECARDS:GCFC2 KEGG:6936 WIKI:GCFC2 lymphoid enhancer-binding factor 1 HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 GENECARDS:LEF1 KEGG:51176 ATLASONC:GC_LEF1 WIKI:LEF1 nuclear factor (erythroid-derived 2)-like 1 TCF11 HUGO:NFE2L1 HGNC:7781 ENTREZ:4779 UNIPROT:Q14494 GENECARDS:NFE2L1 KEGG:4779 ATLASONC:GC_NFE2L1 WIKI:NFE2L1 transcription factor 12 HUGO:TCF12 HGNC:11623 ENTREZ:6938 UNIPROT:Q99081 GENECARDS:TCF12 REACTOME:56728 KEGG:6938 ATLASONC:TCF12ID406 WIKI:TCF12 TEA domain family member 1 (SV40 transcriptional enhancer factor) AA "atrophia areata peripapillary chorioretinal degeneration" TCF13 HUGO:TEAD1 HGNC:11714 ENTREZ:7003 UNIPROT:P28347 GENECARDS:TEAD1 REACTOME:65831 KEGG:7003 ATLASONC:GC_TEAD1 WIKI:TEAD1 TEA domain family member 4 TCF13L1 HUGO:TEAD4 HGNC:11717 ENTREZ:7004 UNIPROT:Q15561 GENECARDS:TEAD4 REACTOME:65837 KEGG:7004 WIKI:TEAD4 hepatocyte nuclear factor 4 alpha MODY MODY1 TCF14 HUGO:HNF4A HGNC:5024 ENTREZ:3172 UNIPROT:P41235 GENECARDS:HNF4A REACTOME:211473 KEGG:3172 ATLASONC:GC_HNF4A WIKI:HNF4A transcription factor 15 (basic helix-loop-helix) HUGO:TCF15 HGNC:11627 ENTREZ:6939 UNIPROT:Q12870 GENECARDS:TCF15 KEGG:6939 ATLASONC:GC_TCF15 WIKI:TCF15 conserved helix-loop-helix ubiquitous kinase TCF16 HUGO:CHUK HGNC:1974 ENTREZ:1147 UNIPROT:O15111 GENECARDS:CHUK REACTOME:57214 KEGG:1147 ATLASONC:GC_CHUK WIKI:CHUK zinc finger protein 354A TCF17 HUGO:ZNF354A HGNC:11628 ENTREZ:6940 UNIPROT:O60765 GENECARDS:ZNF354A REACTOME:65741 KEGG:6940 WIKI:ZNF354A transcription factor 19 HUGO:TCF19 HGNC:11629 ENTREZ:6941 UNIPROT:Q9Y242 GENECARDS:TCF19 KEGG:6941 WIKI:TCF19 transcription factor 20 HUGO:TCF20 HGNC:11631 ENTREZ:6942 UNIPROT:Q9UGU0 GENECARDS:TCF20 KEGG:6942 WIKI:TCF20 transcription factor 21 HUGO:TCF21 HGNC:11632 ENTREZ:6943 UNIPROT:O43680 GENECARDS:TCF21 KEGG:6943 ATLASONC:GC_TCF21 WIKI:TCF21 transcription factor 23 HUGO:TCF23 HGNC:18602 ENTREZ:150921 UNIPROT:Q7RTU1 GENECARDS:TCF23 KEGG:150921 WIKI:TCF23 transcription factor 24 HUGO:TCF24 HGNC:32275 ENTREZ:100129654 UNIPROT:Q7RTU0 GENECARDS:TCF24 KEGG:100129654 WIKI:TCF24 transcription factor 25 HUGO:TCF25 HGNC:29181 ENTREZ:22980 UNIPROT:Q9BQ70 GENECARDS:TCF25 KEGG:22980 ATLASONC:GC_TCF25 WIKI:TCF25 TCF3 TCF4 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: PMID:19623618 PMID:19619488 HNF1 homeobox Phosphorylation sites specific for HIPK2 not known PMID:21285352 References_end</body> </html> </notes> <label text="LEF_TCF*"/> <bbox w="65.0" h="25.0" x="353.6154" y="3060.2307"/> <glyph class="state variable" id="_abecbc7d-dd98-44a4-8b71-6de5b2fc249c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="413.6154" y="3055.7795"/> </glyph> <glyph class="state variable" id="_6d139007-3f22-4b6f-a3d9-e498eecca29d"> <state value="" variable="S40"/> <bbox w="25.0" h="10.0" x="406.1154" y="3078.1145"/> </glyph> <glyph class="state variable" id="_c9936902-1249-4e37-9b0f-2dfcc1f208e4"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="413.6154" y="3067.7307"/> </glyph> <glyph class="state variable" id="_53c7ad06-2194-40ed-ad4d-d636ab48f615"> <state value="" variable="S166"/> <bbox w="30.0" h="10.0" x="339.01556" y="3055.2307"/> </glyph> <glyph class="state variable" id="_28b2d11b-eaab-4508-b459-ca3adbf426a2"> <state value="" variable="T155"/> <bbox w="30.0" h="10.0" x="338.6154" y="3080.0571"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1020_mpk1_mpk1_csa48" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP5:ERK* Identifiers_end</body> </html> </notes> <label text="DUSP5:ERK*"/> <bbox w="85.0" h="90.0" x="707.0" y="3061.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s366_mpk1_mpk1_sa244"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 5 HUGO:DUSP5 HGNC:3071 ENTREZ:1847 UNIPROT:Q16690 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: DUSP5 represents an inducible ERK-specific MKP and it functions as both a nuclear anchor and inactivator of ERK MODULE:MAPK in mammalian cells. PMID:17052211 References_end</body> </html> </notes> <label text="DUSP5"/> <bbox w="60.0" h="27.0" x="721.0" y="3074.0"/> <glyph class="state variable" id="_2b29b4c2-1683-4660-8036-f686202bc15c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="716.0" y="3082.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s370_mpk1_mpk1_sa247"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="60.0" h="27.0" x="726.5" y="3101.0"/> <glyph class="state variable" id="_d9b768e8-c030-457f-a8f3-918c2c78932e"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="721.5" y="3114.205"/> </glyph> <glyph class="state variable" id="_42dcdbfb-a134-4877-a7cd-c908241882dc"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="721.5" y="3104.154"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1024_mpk1_mpk1_csa106" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP1:JNK* Identifiers_end</body> </html> </notes> <label text="DUSP1:JNK*"/> <bbox w="105.0" h="86.0" x="2322.0" y="3025.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s792_mpk1_mpk1_sa547"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 1 PTPN10 HUGO:DUSP1 HGNC:3064 ENTREZ:1843 UNIPROT:P28562 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MKP-1 (DUSP1) preferentially inactivates JNK and P38. DUSP1 play its phosphatase role in the nucleus. PMID:19436832 PMID:17496916 References_end</body> </html> </notes> <label text="DUSP1"/> <bbox w="62.0" h="25.0" x="2344.2856" y="3033.8572"/> <glyph class="state variable" id="_250aacef-0ee8-4423-b639-92c8358ff9ac"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2339.2856" y="3041.3572"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s794_mpk1_mpk1_sa549"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 8 PRKM8 HUGO:MAPK8 HGNC:6881 ENTREZ:5599 UNIPROT:P45983 mitogen-activated protein kinase 9 PRKM9 HUGO:MAPK9 HGNC:6886 ENTREZ:5601 UNIPROT:P45984 mitogen-activated protein kinase 10 PRKM10 HUGO:MAPK10 HGNC:6872 ENTREZ:5602 UNIPROT:P53779 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: mitogen-activated protein kinase 8 PRKM8 HUGO:MAPK8 HGNC:6881 ENTREZ:5599 UNIPROT:P45983 GENECARDS:MAPK8 REACTOME:59293 KEGG:5599 ATLASONC:JNK1ID196 WIKI:MAPK8 mitogen-activated protein kinase 9 PRKM9 HUGO:MAPK9 HGNC:6886 ENTREZ:5601 UNIPROT:P45984 GENECARDS:MAPK9 REACTOME:59295 KEGG:5601 ATLASONC:JNK2ID426 WIKI:MAPK9 mitogen-activated protein kinase 10 PRKM10 HUGO:MAPK10 HGNC:6872 ENTREZ:5602 UNIPROT:P53779 GENECARDS:MAPK10 REACTOME:59297 KEGG:5602 ATLASONC:JNK3ID427 WIKI:MAPK10 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:apoptosis / MODULE:MOMP_REGULATION MAP:apoptosis / MODULE:TNF_RESPONSE MAP:dnarepair / MODULE:G2_M_CHECKPOINT MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="JNK*"/> <bbox w="62.0" h="25.0" x="2352.0" y="3059.8572"/> <glyph class="state variable" id="_4d8eba59-e5e9-40ad-b177-7da7e0b8b91f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2347.0" y="3072.1096"/> </glyph> <glyph class="state variable" id="_9d21b5ed-abba-48c4-998a-d9acc0d37d67"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2347.0" y="3062.6047"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1025_mpk1_mpk1_csa107" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DUSP1:p38* Identifiers_end</body> </html> </notes> <label text="DUSP1:p38*"/> <bbox w="91.0" h="86.0" x="2865.0" y="3051.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s791_mpk1_mpk1_sa546"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: dual specificity phosphatase 1 PTPN10 HUGO:DUSP1 HGNC:3064 ENTREZ:1843 UNIPROT:P28562 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MKP-1 (DUSP1) preferentially inactivates JNK and P38. DUSP1 play its phosphatase role in the nucleus. PMID:19436832 PMID:17496916 References_end</body> </html> </notes> <label text="DUSP1"/> <bbox w="62.0" h="25.0" x="2880.2856" y="3058.8572"/> <glyph class="state variable" id="_f4d7d3a2-93b8-421a-9186-90e0d39282ca"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2875.2856" y="3066.3572"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s793_mpk1_mpk1_sa548"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: mitogen-activated protein kinase 11 PRKM11 HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 mitogen-activated protein kinase 12 SAPK3 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 mitogen-activated protein kinase 13 PRKM13 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 mitogen-activated protein kinase 14 CSBP1 CSBP2 CSPB1 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end Identifiers_begin: mitogen-activated protein kinase 11 PRKM11 HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 GENECARDS:MAPK11 REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11 mitogen-activated protein kinase 12 SAPK3 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 GENECARDS:MAPK12 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12 mitogen-activated protein kinase 13 PRKM13 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 GENECARDS:MAPK13 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13 mitogen-activated protein kinase 14 CSBP1 CSBP2 CSPB1 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 GENECARDS:MAPK14 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14 Mxi2 P38 "P38 MAP kinase" PRKM14 PRKM15 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> Identifiers_begin: mitogen-activated protein kinase 11 PRKM11 HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 GENECARDS:MAPK11 REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11 mitogen-activated protein kinase 12 SAPK3 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 GENECARDS:MAPK12 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12 mitogen-activated protein kinase 13 PRKM13 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 GENECARDS:MAPK13 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13 mitogen-activated protein kinase 14 CSBP1 CSBP2 CSPB1 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 GENECARDS:MAPK14 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14 Mxi2 P38 "P38 MAP kinase" PRKM14 PRKM15 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end</body> </html> </notes> <label text="p38*"/> <bbox w="62.0" h="25.0" x="2889.2856" y="3083.8572"/> <glyph class="state variable" id="_c89e8b6a-2a5a-4f68-bf0f-5fc449db1463"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2884.2856" y="3095.989"/> </glyph> <glyph class="state variable" id="_58cb1285-fed1-40c7-9151-5392fb7ea6a8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2884.2856" y="3086.7832"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1027_mpk1_mpk1_csa109" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:SMAD3:SMAD4 Identifiers_end</body> </html> </notes> <label text="SMAD3:SMAD4"/> <bbox w="100.0" h="80.0" x="3730.0" y="2950.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s920_mpk1_mpk1_sa673"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: SMAD family member 3 "MAD mothers against decapentaplegic homolog 3 (Drosophila)" MADH3 "SMAD mothers against DPP homolog 3 (Drosophila)" HUGO:SMAD3 HGNC:6769 ENTREZ:4088 UNIPROT:P84022 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD3"/> <bbox w="50.0" h="25.0" x="3755.0" y="2957.5"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s915_mpk1_mpk1_sa676"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: SMAD family member 4 "MAD mothers against decapentaplegic homolog 4 (Drosophila)" MADH4 "SMAD mothers against DPP homolog 4 (Drosophila)" HUGO:SMAD4 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD4"/> <bbox w="50.0" h="25.0" x="3755.0" y="2981.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1028_mpk1_mpk1_csa108" compartmentRef="mpk1_mpk1_c4_mpk1_mpk1_ca4"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:SMAD2:SMAD4 Identifiers_end</body> </html> </notes> <label text="SMAD2:SMAD4"/> <bbox w="100.0" h="80.0" x="3610.0" y="2950.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s919_mpk1_mpk1_sa674"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: SMAD family member 2 "MAD mothers against decapentaplegic homolog 2 (Drosophila)" MADH2 "SMAD mothers against DPP homolog 2 (Drosophila)" HUGO:SMAD2 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end Identifiers_begin: SMAD family member 2 "MAD mothers against decapentaplegic homolog 2 (Drosophila)" MADH2 "SMAD mothers against DPP homolog 2 (Drosophila)" HUGO:SMAD2 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 GENECARDS:SMAD2 REACTOME:405890 KEGG:4087 ATLASONC:SMAD2ID370 WIKI:SMAD2 Identifiers_end Maps_Modules_begin: MAP:emtcellmotility / MODULE:EMT_REGULATORS MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD2"/> <bbox w="50.0" h="25.0" x="3635.0" y="2954.5"/> <glyph class="state variable" id="_eb766e1b-2121-4568-b415-63b5ff849596"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3680.0" y="2949.5"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s918_mpk1_mpk1_sa675"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: SMAD family member 4 "MAD mothers against decapentaplegic homolog 4 (Drosophila)" MADH4 "SMAD mothers against DPP homolog 4 (Drosophila)" HUGO:SMAD4 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes. PMID:21614932 References_end</body> </html> </notes> <label text="SMAD4"/> <bbox w="50.0" h="25.0" x="3635.0" y="2979.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1029_mpk1_mpk1_csa65" compartmentRef="mpk1_mpk1_c9_mpk1_mpk1_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GPCR*:GRK* Identifiers_end</body> </html> </notes> <label text="GPCR*:GRK*"/> <bbox w="84.0" h="82.0" x="2114.0" y="2103.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s548_mpk1_mpk1_sa318"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end Identifiers_begin: G protein-coupled receptor kinase 1 HUGO:GRK1 HGNC:10013 ENTREZ:6011 UNIPROT:Q15835 GENECARDS:GRK1 KEGG:6011 ATLASONC:GC_GRK1 WIKI:GRK1 G protein-coupled receptor kinase 4 HUGO:GRK4 HGNC:4543 ENTREZ:2868 UNIPROT:P32298 GENECARDS:GRK4 KEGG:2868 ATLASONC:GC_GRK4 WIKI:GRK4 G protein-coupled receptor kinase 5 HUGO:GRK5 HGNC:4544 ENTREZ:2869 UNIPROT:P34947 GENECARDS:GRK5 REACTOME:55956 KEGG:2869 WIKI:GRK5 G protein-coupled receptor kinase 6 HUGO:GRK6 HGNC:4545 ENTREZ:2870 UNIPROT:P43250 GENECARDS:GRK6 KEGG:2870 ATLASONC:GC_GRK6 WIKI:GRK6 G protein-coupled receptor kinase 7 HUGO:GRK7 HGNC:17031 ENTREZ:131890 UNIPROT:Q8WTQ7 GENECARDS:GRK7 KEGG:131890 WIKI:GRK7 adrenergic beta receptor kinase 1 HUGO:ADRBK1 HGNC:289 ENTREZ:156 UNIPROT:P25098 GENECARDS:ADRBK1 REACTOME:50271 KEGG:156 ATLASONC:GC_ADRBK1 WIKI:ADRBK1 adrenergic beta receptor kinase 2 HUGO:ADRBK2 HGNC:290 ENTREZ:157 UNIPROT:P35626 GENECARDS:ADRBK2 KEGG:157 ATLASONC:GC_ADRBK2 WIKI:ADRBK2 Identifiers_end Maps_Modules_begin: MAP:survival / MODULE:HEDGEHOG MAP:survival / MODULE:MAPK Maps_Modules_end References_begin: PMID:16525728 PMID:15618519 Recruited GRKs (GRK2 and GRK3) phosphorylate GPCR and increase its affinity for binding beta-ARRESTIN. PMID:11226259 References_end</body> </html> </notes> <label text="GRK*"/> <bbox w="50.0" h="25.0" x="2131.8333" y="2135.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s815_mpk1_mpk1_sa577"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: G protein-coupled receptor 1 HUGO:GPR1 HGNC:4463 ENTREZ:2825 UNIPROT:P46091 G protein-coupled receptor 3 HUGO:GPR3 HGNC:4484 ENTREZ:2827 UNIPROT:P46089 G protein-coupled receptor 4 HUGO:GPR4 HGNC:4497 ENTREZ:2828 UNIPROT:P46093 G protein-coupled receptor 6 HUGO:GPR6 HGNC:4515 ENTREZ:2830 UNIPROT:P46095 G protein-coupled receptor 12 HUGO:GPR12 HGNC:4466 ENTREZ:2835 UNIPROT:P47775 G protein-coupled receptor 15 HUGO:GPR15 HGNC:4469 ENTREZ:2838 UNIPROT:P49685 G protein-coupled receptor 17 HUGO:GPR17 HGNC:4471 ENTREZ:2840 UNIPROT:Q13304 G protein-coupled receptor 18 HUGO:GPR18 HGNC:4472 ENTREZ:2841 UNIPROT:Q14330 G protein-coupled receptor 19 HUGO:GPR19 HGNC:4473 ENTREZ:2842 UNIPROT:Q15760 G protein-coupled receptor 20 HUGO:GPR20 HGNC:4475 ENTREZ:2843 UNIPROT:Q99678 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylation of GPCR (by GRK) induces the activation of ERK cascade on eary endosomes. PMID:19565474 References_end</body> </html> </notes> <label text="GPCR*"/> <bbox w="50.0" h="25.0" x="2132.818" y="2111.9092"/> <glyph class="state variable" id="_88c15f53-0bbb-4995-b874-7f7f711cd38a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2127.818" y="2119.4092"/> </glyph> <glyph class="unit of information" id="_5a5154dc-2e87-4a56-a0dc-e07a38b317dd"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2135.318" y="2106.9092"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1030_mpk1_mpk1_csa27" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="KSR1:MEK*"/> <bbox w="112.0" h="108.0" x="1687.0" y="1838.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s237_mpk1_mpk1_sa148"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="41.0" h="77.0" x="1697.0" y="1849.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s238_mpk1_mpk1_sa149"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1740.5" y="1874.5"/> <glyph class="state variable" id="_6e012b78-acf2-47c0-8870-9d567a1b5949"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1735.5" y="1886.1664"/> </glyph> <glyph class="state variable" id="_d5f6a6f3-8637-4bee-b614-7a9e1e9fbd51"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1735.5" y="1877.6261"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1031_mpk1_mpk1_csa26" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:KSR1-CTER*:MEK* Identifiers_end</body> </html> </notes> <label text="KSR1-CTER*:MEK*"/> <bbox w="134.0" h="85.0" x="2016.0" y="1871.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s213_mpk1_mpk1_sa131"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is cleaved by CASPASE3 in two regions: the C-ter region which mediates MEK binding and the N-ter region which contains the ERK binding site and the C1 domain required for plasma membrane localisation PMID:17613518 References_end</body> </html> </notes> <label text="KSR1-CTER*"/> <bbox w="119.0" h="26.0" x="2023.0" y="1880.0"/> <glyph class="unit of information" id="_98ea1947-d558-4009-a7a7-73ede59633bb"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="2057.5" y="1875.0"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s214_mpk1_mpk1_sa132"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="66.0" h="26.0" x="2055.5" y="1906.5"/> <glyph class="state variable" id="_c0135b82-8987-499a-a288-706963ae5b44"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2050.5" y="1918.833"/> </glyph> <glyph class="state variable" id="_aed36447-d6ad-42ca-a9b7-12a5d6685ea6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2050.5" y="1909.951"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1032_mpk1_mpk1_csa10" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IMP*:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="IMP*:KSR1:MEK*"/> <bbox w="163.0" h="109.0" x="2246.5" y="1896.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s80_mpk1_mpk1_sa60"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="49.0" h="76.0" x="2304.5" y="1906.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s81_mpk1_mpk1_sa61"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="2349.5" y="1932.0"/> <glyph class="state variable" id="_e411be08-fede-4a6e-bc42-a1c22c8145dc"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2344.5" y="1943.6664"/> </glyph> <glyph class="state variable" id="_fe0d2cf4-6b7b-4034-b957-b5d253fe55c5"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2344.5" y="1935.1261"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s234_mpk1_mpk1_sa146"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: BRCA1 associated protein HUGO:BRAP HGNC:1099 ENTREZ:8315 UNIPROT:Q7Z569 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: IMP (BRAP) is a RasGTP-interacting protein. It is constitutively bound to KSR1 blocking the enhancement of ERK activation (KSR1 is kept in an inactivated state) maybe recruiting KSR1 to microdomains inaccessible to activators of its function. This could be a mechanism to limit the engagement of ERK cascade in the absence of Ras activation. PMID:14724641 References_end</body> </html> </notes> <label text="IMP*"/> <bbox w="50.0" h="25.0" x="2254.5" y="1931.5"/> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1033_mpk1_mpk1_csa61" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="ERK*:KSR1:MEK*"/> <bbox w="136.0" h="110.0" x="1623.0" y="2034.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s519_mpk1_mpk1_sa298"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="50.0" h="25.0" x="1637.3334" y="2042.6667"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s520_mpk1_mpk1_sa299"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1683.3334" y="2069.6667"/> <glyph class="state variable" id="_16aaf359-a600-44c1-8097-343716ec1aec"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2081.333"/> </glyph> <glyph class="state variable" id="_78fa69b0-9958-43fa-81a9-338da27e9f69"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2072.7927"/> </glyph> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s521_mpk1_mpk1_sa300"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body>Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="1683.3334" y="2094.6667"/> <glyph class="state variable" id="_d1c97124-7b19-47cd-b94b-b911096839bc"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2106.5234"/> </glyph> <glyph class="state variable" id="_681d90ac-9f22-4198-8588-8727991a7d4c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1675.8334" y="2097.2168"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1034_mpk1_mpk1_csa62" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ERK*:KSR1:MEK* Identifiers_end</body> </html> </notes> <label text="ERK*:KSR1:MEK*"/> <bbox w="134.0" h="112.0" x="1835.0" y="2058.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s526_mpk1_mpk1_sa303"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: kinase suppressor of ras 1 "kinase suppressor of ras" KSR HUGO:KSR1 HGNC:6465 ENTREZ:8844 UNIPROT:Q8IVT5 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: KSR1 is a scaffold protein for ERK cascade. It normally localises in the cytosol but after GF treatment it moves to the plasma membrane. Its interaction with MEK1/2 is constitutive. Under endogenous conditions KSR1 facilitates the association of MEK and B-Raf (and not C-Raf) thus promoting MEK and ERK activation (on plasma membrane). PMID:19541618 References_end</body> </html> </notes> <label text="KSR1"/> <bbox w="50.0" h="25.0" x="1852.6666" y="2069.6667"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s527_mpk1_mpk1_sa304"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase 1 PRKMK1 HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 mitogen-activated protein kinase kinase 2 PRKMK2 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1). MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19565474 PMID:17178906 PMID:15547943 References_end</body> </html> </notes> <label text="MEK*"/> <bbox w="50.0" h="25.0" x="1896.6666" y="2093.6667"/> <glyph class="state variable" id="_a92fe4ce-d1ff-4891-a5d0-a510f3dbe38c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.1666" y="2105.333"/> </glyph> <glyph class="state variable" id="_5d449f91-4ed1-4335-8531-f89e125f39fb"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.1666" y="2096.7927"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="mpk1_mpk1_s530_mpk1_mpk1_sa307"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Modelling choices: - ERK represents both ERK1 and ERK2 because it is not completely clear when the two isoforms behave differently. This also happens for the activation on late endosomes: it is known that only ERK1 is activated there, however when ERK1 reaches nucleus, it behaves like ERK2. - Once activated, ERK may either keep being in complex with its activators and scaffolds, or be released in the cytoplasm. In the latter case, it may either dimerise, being able to activate its cytoplasmic targets, or not, being able to translocate to the nucleus. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end Identifiers_begin: mitogen-activated protein kinase 1 PRKM1 PRKM2 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 mitogen-activated protein kinase 3 PRKM3 HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 mitogen-activated protein kinase 4 HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 mitogen-activated protein kinase 6 HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 ERK, ERK2, MAPK2, p41mapk Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:CASPASES MAP:apoptosis / MODULE:MOMP_REGULATION MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission. In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins. MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes) PMID:19541618 PMID:19565474 PMID:15547943 References_end</body> </html> </notes> <label text="ERK*"/> <bbox w="50.0" h="25.0" x="1897.0834" y="2119.1667"/> <glyph class="unit of information" id="_72092276-8367-4983-b74d-f2d4d32c4098"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="1912.0834" y="2114.1667"/> </glyph> <glyph class="state variable" id="_02994043-9360-4421-8cdb-167e4aeee07c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.5834" y="2131.0234"/> </glyph> <glyph class="state variable" id="_2cb57c32-95a6-4414-a50c-0c794abc5d39"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1889.5834" y="2121.7168"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1035_mpk1_mpk1_csa95" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GADD45*:MAP3K4 Identifiers_end</body> </html> </notes> <label text="GADD45*:MAP3K4"/> <bbox w="127.0" h="84.0" x="3871.9963" y="2233.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s738_mpk1_mpk1_sa511"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: growth arrest and DNA-damage-inducible alpha DDIT1 HUGO:GADD45A HGNC:4095 ENTREZ:1647 UNIPROT:P24522 growth arrest and DNA-damage-inducible beta MYD118 HUGO:GADD45B HGNC:4096 ENTREZ:4616 UNIPROT:O75293 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: Expression of GADD45 is the culmination of a signalling pathway that requires prior expression of the tumour suppressor protein P53 which trans-activates the gadd45 gene. P53 expression is in turn driven by the activity of the ATM gene product. GADD45alpha/beta are direct MEKK4 interactors. They are involved in genotoxin regulation of MEKK4 signalling to JNK and P38. PMID:11274345 References_end</body> </html> </notes> <label text="GADD45*"/> <bbox w="75.0" h="25.0" x="3904.4963" y="2239.6667"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s739_mpk1_mpk1_sa512"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: mitogen-activated protein kinase kinase kinase 4 MEKK4 HUGO:MAP3K4 HGNC:6856 ENTREZ:4216 UNIPROT:Q9Y6R4 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: MEKK4 is a MAP3K and can activate both JNK and P38 pathways. It may be an effector for stress pathways activated by genotoxins. PMID:11274345 References_end</body> </html> </notes> <label text="MAP3K4"/> <bbox w="73.0" h="26.0" x="3901.4963" y="2263.6667"/> <glyph class="state variable" id="_743f2a0c-1013-4c8a-9013-09cca78f56a5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="3893.9963" y="2271.6667"/> </glyph> </glyph> </glyph> <glyph class="complex" id="mpk1_mpk1_s1036_mpk1_mpk1_csa82" compartmentRef="mpk1_mpk1_c1_mpk1_mpk1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TAB*:TAK1*:TGFBR1:TGFBR2 Identifiers_end</body> </html> </notes> <label text="TAB*:TAK1*:TGFBR1:TGFBR2"/> <bbox w="199.0" h="85.0" x="3626.9963" y="2238.0"/> <glyph class="macromolecule" id="mpk1_mpk1_s58_mpk1_mpk1_sa459"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: TGF-beta activated kinase 1/MAP3K7 binding protein 1 MAP3K7IP1 "mitogen-activated protein kinase kinase kinase 7 interacting protein 1" HUGO:TAB1 HGNC:18157 ENTREZ:10454 UNIPROT:Q15750 TGF-beta activated kinase 1/MAP3K7 binding protein 2 MAP3K7IP2 "mitogen-activated protein kinase kinase kinase 7 interacting protein 2" HUGO:TAB2 HGNC:17075 ENTREZ:23118 UNIPROT:Q9NYJ8 TGF-beta activated kinase 1/MAP3K7 binding protein 3 MAP3K7IP3 "mitogen-activated protein kinase kinase kinase 7 interacting protein 3" HUGO:TAB3 HGNC:30681 ENTREZ:257397 UNIPROT:Q8N5C8 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TAK1 is the only MAP3K that requires the adapter proteins TAB123 for its activation. PMID:20060931 References_end</body> </html> </notes> <label text="TAB*"/> <bbox w="50.0" h="25.0" x="3668.163" y="2271.0"/> </glyph> <glyph class="macromolecule" id="mpk1_mpk1_s59_mpk1_mpk1_sa460"> <notes> <html xmlns="http://www.sbml.org/sbml/level2/version4" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <body> <html> <body>Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 TAK1 HUGO:MAP3K7 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 Identifiers_end Maps_Modules_begin: MAP:mpk1 / MODULE:MAPK Maps_Modules_end References_begin: TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways. Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6. PMID:18855897 PMID:11274345 References_end Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 TAK1 HUGO:MAP3K7 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 GENECARDS:MAP3K7 REACTOME:168070 KEGG:6885 ATLASONC:MAP3K7ID454ch6q15 WIKI:MAP3K7 MEKK7 MEKK7 TAK1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways. Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6. PMID:18855897 PMID:11274345 References_end</body> </html> Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 TAK1 HUGO:MAP3K7 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 GENECARDS:MAP3K7 REACTOME:168070 KEGG:6885 ATLASONC:MAP3K7ID454ch6q15 WIKI:MAP3K7 MEKK7 MEKK7 TAK1 Identifiers_end Maps_Modules_begin: MAP:apoptosis / MODULE:AKT_MTOR MAP:apoptosis / MODULE:TNF_RESPONSE MAP:survival / MODULE:MAPK MAP:survival / MODULE:WNT_CANONICAL MAP:survival / MODULE:WNT_NON_CANONICAL Maps_Modules_end References_begin: TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways. Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6. 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