FGFR Substrate 2

Encoded by human FRS2 Gene, 508-aa 56.8-kD FGFR Substrate 2 contains a myristylation sequence, a PTB domain, and 4 potential GRB2/SHP2-binding sites. FGFR-mediated Tyr-phosphorylated FRS2 binds to FGFR1 and GRB2/SOS in response to FGF or NGF. An FGFR1 juxtamembrane segment and the PTB domain appear to interact and mediate FRS Tyr phosphorylation. Myristylation is essential for FRS2 membrane localization, Tyr phosphorylation, GRB2/SOS recruitment, and MAPK activation. FRS2A is Thr phosphorylated by MAPK in response to FGF, insulin, EGF, and PDGF. FRS2 may function as a lipid-anchored docking protein that targets signaling molecules to the plasma membrane in response to FGF to link receptor activation with MAPK and other pathways essential for cell growth and differentiation. (NCI Thesaurus)

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