A LIPID-ANCHORED GRB2-BINDING PROTEIN THAT LINKS FGF-RECEPTOR ACTIVATION TO THE RAS MAPK SIGNALING PATHWAY/

Activation of the Ras/MAPK signaling cascade is essential for growth f actor-induced cell proliferation and differentiation. In this report, we describe the purification, cloning, and characterization of a novel protein, designated FRS2, that is tyrosine phosphorylated and binds t o Grb2/Sos in response to FGF or NGF stimulation. We find that FRS2 is myristylated and that this modification is essential for membrane loc alization, tyrosine phosphorylation, Grb2/Sos recruitment, and MAPK ac tivation. FRS2 functions as a lipid-anchored docking protein that targ ets signaling molecules to the plasma membrane in response to FGF stim ulation to link receptor activation with the MAPK and other signaling pathways essential for cell growth and differentiation. Finally, we de monstrate that FRS2 is closely related and probably indentical to SNT, the long-sought target of FGF and NGF receptors.