c-SRC*

Protein c-SRC* map

Identifiers
c-src tyrosine kinase
HUGO:CSK HGNC:2444 ENTREZ:1445 UNIPROT:P41240 GENECARDS:CSK REACTOME:52852 ATLASONC:GC_CSK WIKI:CSK

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / CELL_CELL_ADHESIONS  map
 EMT  map  / ADHERENS_JUNCTIONS  map

References
PMID:18829532
PMID:9819392
PTK6 and CSK both can phosphorylate ARHGAP35 (p190) at Y1105
RasGAP actvity of RASA1 is reduced when associated with ARHGAP35 which is a specific GAP for RhoA
ARHGAP35 is tyrosine-phosphorylated.
The association of ARHGAP35 (p190) with RASA1 (p120) is promoted and stabilized by phosphorylation of p190 at Y1105 by CSK or by PTK6.

c-SRC*@Cytoplasm

References
e_re1636( EMT  map ):
PMID:21776389
Src participates in the activation of various downstream signaling pathways through molecular interactions with growth factor receptors such as the epidermal growth factor receptor (EGFR) family, hepatocyte growth factor receptor (Met), integrin cell adhesion receptors

c-SRC*|​Y_pho|​active@Cytoplasm

References
e_re1636( EMT  map ):
PMID:21776389
Src participates in the activation of various downstream signaling pathways through molecular interactions with growth factor receptors such as the epidermal growth factor receptor (EGFR) family, hepatocyte growth factor receptor (Met), integrin cell adhesion receptors
e_re387( EMT  map ):
PMID:9069260
Activated HRAS (GTP bound forn) is associated with the plasma membrane.
Inactive RAF1 is associated in the cytoplasm with YWHAB via S259 phosphorylation site and also binding site.
RAF1 has a RAS-binding Cysteine-rich domain (CRD) and an additional RAS-binding domain (RBD).
RAF1 binds activated HRAS via the RBD. This binding displaces YWHAB from Ser259 and unmasks the CRD.
YWHAB has been displaced from S259 may now bind its higher affinity S621 site.
This stabilises an OPEN RAF1 conformation that is catalytically active.
Active and open RAF1 binds to RAS via both CRD and RBD domains.
An unidentified protein tyrosine kinase located in the plasma membrane phosphorylates tyrosine residues at 340 and 341.
This Tyrosine phosphorylation serves to further stabilise the active OPEN RAF1 conformation.
While the kinase has not been definitively identified, SRC is a plausible candidate. RAF1 interacts with SRC and co-immunoprecipates with SRC-FYN.
PIN1, a prolyl isomerase converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A.
Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: S338, Y374 and T491
e_re931( EMT  map ):
PMID:18829532
PMID:9819392
PTK6 and CSK both can phosphorylate ARHGAP35 (p190) at Y1105
RasGAP actvity of RASA1 is reduced when associated with ARHGAP35 which is a specific GAP for RhoA
ARHGAP35 is tyrosine-phosphorylated.
The association of ARHGAP35 (p190) with RASA1 (p120) is promoted and stabilized by phosphorylation of p190 at Y1105 by CSK or by PTK6.
e_re977( EMT  map ):
Autophosphorylation of PTK2:
PMID:7529872
PMID:19339212
PMID:7657702
PMID:16919435
Autophosphorylation of PTK2 at Y397 creates binding site for CSK, a member of Scr family kinases.
In response to integrin engagement with the ECM, FAK is autophosphorylated predominantly on Y397
This Y397 is the consensus binding site for the SH2 domain of c-Src (CSK)
PMID:11114741
Interaction of CSK with FAK leads to phosphorylation of FAK on other tyrosine residues including Y407, 576, 577, 861, 925/
These phosphorylation events promote PTK2 to its maximal catalytic activity.
Upon autophosphorylation of FAK, a signaling complex of FAK, CSK binds to and can phosphorylate various adaptor proteins such as p130Cas and paxillin.
e_re1272( EMT  map ):
PMID:17673906
Upon TGFB stimulation, the activated TGFBR1 recruits and directly phosphorylates SHC1 on tyrosine and serine.
TGFB-induced SHC1 phosphorylation induces SHC1 association with Grb2 and Sos
PMID:12767520
Upon IGF stimulation, the activated IGF1R recruits and directly phosphorylates SHC1, leading to cellular proliferation
e_re1627( EMT  map ):
PMID:24376839
PTP4A3 is implicated in cell adhesion and the regulation of focal adhesion components including integrin beta-1, Src, paxillin and p130Cas
Similarly, PTP4A3 promotes cell invasion by increasing MMP2 activity and decreasing the expression of the MMP inhibitor, TIMP2.
PTP4A3 is also involved in EMT: PTP4A3 overexpression in colorectal carcinoma cells downregulates epithelial markers (E-cadherin, plakoglobin, and integrin beta-3) and upregulates expression of mesenchymal markers (fibronectin and snail1).
PMID:23691193
Src-mediated phosphorylation of PTP4A3 Is required for Rho activation, motility and invasion promoted by PTP4A3.
http://d-scholarship.pitt.edu/18634/1/Zimmerman_ETD-2013.pdf
c-MYC activity was able to increase Ptp4a3 gene expression in a fibroblast cell culture model.
Tumors from the Ptp4a3-null mice had elevated levels of both IGF1Rβ and c-MYC compared to tumors replete with PTP4A3.
Ptp4a3-null cells displayed less migration compared to wildtype cells and loss of VEGF-induced phosphorylation of SRC protein.
Reduced migration and SRC activation were also observed when human endothelial cells were treated with a small molecule inhibitor of PTP4A3.
e_re1632( EMT  map ):
PMID:16371504
N-cadherin is phosphorylated by c-Src at Tyr-820, Tyr-853, Tyr-860, Tyr-884, and Tyr-886.
Phosphorylation of Tyr-860 (Tyr-835 in E-cadherin) can disrupt cadherin binding to beta-catenin


Modifications:
In compartment: Cytoplasm
  1. c-SRC*@Cytoplasm map

  2. c-SRC*|​Y_pho|​active@Cytoplasm map

Participates in complexes:
In compartment: Cytoplasm

  1. FAK1*|​Y_pho|​pho:​c-SRC*@Cytoplasm map

  2. BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  3. Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  4. Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​ZYX:​c-SRC*@Cytoplasm map
  5. ARP2_3*:​Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map

Participates in reactions:
As Reactant or Product:

  1. c-SRC*@Cytoplasm map map c-SRC*|​Y_pho|​active@Cytoplasm map

  2. Src family kinases*@Cytoplasm map map c-SRC*|​Y_pho|​active@Cytoplasm map
  3. FAK1*|​Y_pho|​pho|​active@Cytoplasm map + c-SRC*|​Y_pho|​active@Cytoplasm map map FAK1*|​Y_pho|​pho:​c-SRC*@Cytoplasm map
  4. FAK1*|​Y_pho|​pho:​c-SRC*@Cytoplasm map + BCAR1@Cytoplasm map + Talin*@Cytoplasm map + PXN|​pho@Cytoplasm map + Vinculin*@Cytoplasm map map BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  5. BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map + Actinin*@Cytoplasm map + Actin cytoskeletal*@Cytoplasm map map Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  6. Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map + ZYX@Cytoplasm map map Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​ZYX:​c-SRC*@Cytoplasm map
  7. ARP2_3*@Cytoplasm map + Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map map ARP2_3*:​Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  8. ARP2_3*:​Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map map Actin polymerization@Nucleus map

As Catalyser:

  1. SHC1_p66_p52*@Cytoplasm map map SHC1_p66_p52*|​Y_pho|​S_pho|​active@Cytoplasm map

  2. EGF family*:​EGFR family*|​hm2@Cytoplasm map map EGF family*:​EGFR family*|​pho|​hm2@Cytoplasm map
  3. STAT3@Cytoplasm map map STAT3|​pho|​active@Cytoplasm map
  4. PTP4A3@Cytoplasm map map PTP4A3|​pho|​active@Cytoplasm map
  5. E-Cadherin*@Cytoplasm map map E-Cadherin*|​Y_pho@Cytoplasm map
  6. GTP:​RAF1|​S259_pho|​S621_pho|​S_pho|​open:​YWHAB@Cytoplasm map + ATP@Cytoplasm map map RAF1|​S259_pho|​S621_pho|​Y340_pho|​Y341_pho|​open@Cytoplasm map + ADP@Cytoplasm map
  7. ARHGAP35@Cytoplasm map map ARHGAP35|​pho@Cytoplasm map
  8. FAK1*|​pho@Cytoplasm map map FAK1*|​Y_pho|​pho|​active@Cytoplasm map
  9. PXN@Cytoplasm map map PXN|​pho@Cytoplasm map

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