The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1

摘要: Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve and insulin, transmit intracellular signals through Ras proteins. Ligand binding to stimulates guanine-nucleotide-exchange activity increases level of GTP-bound Ras, suggesting that these kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans Drosophila, genetic studies have shown activation by requires Sem-5/drk, which contains single Src-homology (SH) 2 domain two flanking SH3 domains. Sem-5 is homologous mammalian Grb2, binds autophosphorylated EGF receptor other phosphotyrosine-containing proteins Shc its SH2 domain. Here we show in rodent fibroblasts, domains Grb2 are bound proline-rich carboxy-terminal tail mSos1, Drosophila Sos. Sos required signalling central related known Ras-GNRPs. stimulation induces Grb2-mSos1 complex receptor, mSos1 phosphorylation. therefore appears link Ras-GNRP cells.