ASSOCIATION OF SOS RAS EXCHANGE PROTEIN WITH GRB2 IS IMPLICATED IN TYROSINE KINASE SIGNAL TRANSDUCTION AND TRANSFORMATION

The proteins Grb2-Sem-5, Shc and Sos have been implicated in the signa lling pathway from tyrosine kinase receptors to Ras. Grb2-Sem-5 binds directly to murine Sos1, a Ras exchange factor, through two SH3 domain s. Sos is also associated with ligand-activated tyrosine kinase recept ors which bind Grb2-Sem-5, and with the Grb2-Sem-5 binding protein, Sh c. Ectopic expression of Drosophila Sos stimulates morphological trans formation of rodent fibroblasts. These data define a pathway by which tyrosine kinases act through Ras to control cell growth and differenti ation.