Pronk G J, McGlade J, Pelicci G, Pawson T, Bos J L
Laboratory for Physiological Chemistry, University of Utrecht, The Netherlands.
J Biol Chem. 1993 Mar 15;268(8):5748-53.
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.
shc基因的产物似乎是活化致癌酪氨酸激酶（如v-Src和v-Fps）以及活化酪氨酸激酶受体（如表皮生长因子（EGF）和血小板衍生生长因子（PDGF）受体）的底物。我们研究了Shc蛋白是否是活化胰岛素受体酪氨酸激酶的作用靶点。在此我们表明，在表达高水平人胰岛素受体的成纤维细胞中，胰岛素受体激活后，46 kDa和52 kDa的Shc蛋白会迅速磷酸化。此外，我们观察到一种23 kDa的蛋白与Shc蛋白发生胰岛素诱导的结合。这些对Shc蛋白的作用与EGF和PDGF处理后观察到的作用相似。与观察到的Shc-EGF受体结合情况相反，我们未检测到Shc蛋白与胰岛素受体之间的结合。我们得出结论，Shc蛋白是EGF、PDGF和胰岛素共有的信号转导途径中的共同元件。
