Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins.

摘要: The mammalian SHC gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc are phosphorylated on tyrosine by variety of receptor and cytoplasmic kinases. Phosphorylated form complex with the SH2-SH3 containing Grb2 protein is implicated in regulation Ras, suggesting that involved intracellular transmission growth signals from activated kinases to Ras. Overexpression cultured fibroblasts induces transformed phenotype. We now report that, vitro, high affinity binding requires phosphorylation at Tyr317, lies within motif for domain, pYVNV, where Asn +2 position crucial formation. In vivo, Tyr317 major, but not only, site phosphorylation, sole Grb2. Mutant substitution Phe lose capacity be highly upon factor activation, bind induce neoplastic transformation. contrast, have an extensive aminoterminal deletion, retain domain conserve phosphorylated, cell These data indicate formation Shc-Grb2 event transformation induced overexpression support notion can deliver activation RAS.