The Sos (son of sevenless) gene was originally identified in Drosophila, and two mammalian homologues (mSos1 and mSos2) were isolated from a mouse cDNA library. These two cDNAs predict proteins that are approximately 70% identical in their amino acid residues. Both mSos1 and mSos2 are expressed in a wide number of mouse embryonic and adult tissues as well as in several cell lines. The human homologues, hSos1 and hSos2 have also been isolated and show a very high degree of amino acid identity to the mouse genes (98% for Sos1). Sos1 has a predicted molecular weight of 150kDa, but the apparent molecular weight is closer to 170 kDa, presumably due to a high proline content. The mammalian Sos1 protein has a highly specific guanine nucleotide exchange activity toward p21ras . In EGF-stimulated cells, Sos1 interacts with the SH3 domains of GRB2, and GRB2 binds via its SH2 domain to tyrosine 1068 of the activated EGF receptor. Thus, GRB2 recruits Sos1 to the plasma membrane and enables it to activate the Ras signaling pathway by enhancing GTP loading on p21ras .