Insulin-induced phosphorylation of the 46- and 52-kDa Shc proteins.

The products of the shc gene appear to be substrates for activated oncogenic tyrosine kinases, such as v-Src and v-Fps and activated tyrosine kinase receptors like the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors. We investigated whether the Shc proteins are targets for the activated insulin receptor tyrosine kinase. Here we show that the 46- and 52-kDa Shc proteins are rapidly phosphorylated upon insulin receptor activation in fibroblasts expressing elevated levels of human insulin receptors. Furthermore, we observed insulin-induced association of a 23-kDa protein with the Shc proteins. These effects on Shc proteins are similar to those observed after EGF and PDGF treatment. In contrast to the observed Shc-EGF receptor association, we did not detect association between the Shc proteins and the insulin receptor. We conclude that the Shc proteins are common elements in a signal transduction pathway that is shared by EGF, PDGF, and insulin.