THE CLONING OF GRB10 REVEALS A NEW FAMILY OF SH2 DOMAIN PROTEINS

SH2 domains function to bind proteins containing phosphotyrosine and a re components of proteins that are important signal transducers for ty rosine kinases. We have cloned SH2 domain proteins by screening bacter ial expression libraries with the tyrosine phosphorylated carboxytermi nus of the epidermal growth factor (EGF) receptor. Here we report the identification of a new SH2 domain protein, Grb10, Grb10 is highly rel ated to Grb7, an SH2 domain protein that we have previously identified , In addition to an SH2 domain, Grb7 and Grb10 have a central domain w ith similarity to a putative C, elegans gene likely to be involved in neuronal migration. At least three forms of Grb10 exist in fibroblasts apparently due to alternate translational start sites, Grb10 undergoe s serine but not tyrosine phosphorylation after EGF treatment resultin g in a shift mobility in a large fraction of Grb10 molecules, However Grb10 appears to bind poorly to EGF-Receptor and the true binding part ner for the Grb10 SH2 domain is unclear, Grb10 maps to mouse chromosom e 11 very close to the EGF-Receptor which is remarkably similar to Grb 7 that maps near the EGF-Receptor related HER2 receptor, The finding o f multiple family members with evolutionarily conserved domains indica tes that these SH2 domain proteins are likely to have an important, al though as of yet, unidentified function.