FRS2

Protein FRS2 map

Identifiers
fibroblast growth factor receptor substrate 2
HUGO:FRS2 HGNC:16971 ENTREZ:10818 UNIPROT:Q8WU20 GENECARDS:FRS2 REACTOME:170961 KEGG:10818 ATLASONC:GC_FRS2 WIKI:FRS2

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Survival  map  / MAPK  map

References
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

FRS2@Plasma Membrane

References
s_mpk1_re273( Survival  map ):
FGF stimulation leads to phosphorylation of Shp2 on a tyrosine residue that forms a complex with an additional molecule of Grb2. Grb2/Sos complexes are thus recruited directly and indirectly via Shp2 upon tyrosine phosphorylation of FRS2a in response to growth factor stimulation.
FGF-induced tyrosine phosphorylation of FRS2 results in complex formation with the adaptor protein Grb2 bound to Cbl by means of its SH3 domains. FGF-induced ternary complex formation among FRS2 Grb2 and Cbl results in ubiquitination and degradation of FRS2 and FGF receptor (FGFR).
Spry is induced by activated ERK through phosphorylation on Tyr55. It positively regulates EGFR signalling by sequestering Cbl whereas it negatively regulates FGFR signalling by sequestering Grb2 from FSR2.
PMID:11447289 PMID:11997436 PMID:15173823

FRS2|​pho@Plasma Membrane

References
s_mpk1_re273( Survival  map ):
FGF stimulation leads to phosphorylation of Shp2 on a tyrosine residue that forms a complex with an additional molecule of Grb2. Grb2/Sos complexes are thus recruited directly and indirectly via Shp2 upon tyrosine phosphorylation of FRS2a in response to growth factor stimulation.
FGF-induced tyrosine phosphorylation of FRS2 results in complex formation with the adaptor protein Grb2 bound to Cbl by means of its SH3 domains. FGF-induced ternary complex formation among FRS2 Grb2 and Cbl results in ubiquitination and degradation of FRS2 and FGF receptor (FGFR).
Spry is induced by activated ERK through phosphorylation on Tyr55. It positively regulates EGFR signalling by sequestering Cbl whereas it negatively regulates FGFR signalling by sequestering Grb2 from FSR2.
PMID:11447289 PMID:11997436 PMID:15173823
s_mpk1_re25( Survival  map ):
Grb2 is recruited to the plasma membrane by activated RTKs.
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.
PKC may cause phosphorylation of EGFR leading to a decrease in its activity.
PMID:17496910 PMID:15567848 PMID:11447289 PMID:6321473
s_s_mpk1_re25( Survival  map ):


Modifications:
In compartment: Cytoplasm
  1. FRS2@Cytoplasm map

  2. FRS2|​pho|​active@Cytoplasm map

In compartment: Plasma Membrane

  1. FRS2@Plasma Membrane map

  2. FRS2|​pho@Plasma Membrane map

Participates in complexes:
In compartment: Cytoplasm

  1. FGFR family*:​FRS2|​pho:​GRB2:​SOS*@Cytoplasm map

Participates in reactions:
As Reactant or Product:

  1. FRS2@Cytoplasm map map FRS2|​pho|​active@Cytoplasm map

  2. FRS2|​pho|​active@Cytoplasm map + FGF family*|​hm2:​FGFR family*:​Heparin|​hm2@Cytoplasm map + GRB2@Cytoplasm map + SOS*@Cytoplasm map + PTPN11|​pho|​active@Cytoplasm map map FGFR family*:​FRS2|​pho:​GRB2:​SOS*@Cytoplasm map
  3. FRS2@Plasma Membrane map map FRS2|​pho@Plasma Membrane map

As Catalyser:

  1. s_s_mpk1_s1009 + RTK*@Plasma Membrane map map GRB2:​RTK*:​SOS*@Plasma Membrane map

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