The GRB2/Sem‐5 adaptor protein

GRB2/Sem-5 is a 25-kDa adaptor protein which contains a central Src homology type 2 (SH2) domain flanked by two Src homology type 3 (SH3) domains. GRB2/Sem-5 was first identified due to the essential role of the sem-5 gene product in the vulval induction pathway in Caenorhabditis elegans. The SH2 domain of GRB2/Sem-5 binds to a number of tyrosine phosphorylated proteins, most notably the epidermal growth factor receptor, the insulin receptor substrate IRS-1 and another putative adaptor protein, Shc. The SH3 domains bind to Sos, a guanine nucleotide exchange factor for Ras proteins. GRB2/Sem-5 brings together Sos and tyrosine phosphoproteins into a complex and thereby may regulate the nucleotide exchange rate of Ras and hence its activation state.