Segatto O, Pelicci G, Giuli S, Digiesi G, Di Fiore P P, McGlade J, Pawson T, Pelicci P G
Laboratorio di Immunologia, Istituto Regina Elena, Italy.
Oncogene. 1993 Aug;8(8):2105-12.
The shc genes encodes three widely expressed proteins of 46, 52 and 66 kDa. Overexpression of p46shc and p52shc in NIH3T3 fibroblasts induces a tumorigenic phenotype. Shc products are phosphorylated on tyrosine by the activated epidermal growth factor receptor (EGFR) and become physically associated with EGFR via their SH2 domain. Thus Shc oncoproteins may play a role in mitogenic signal transduction. Here we report that Shc products are substrates also of the erbB-2 kinase and form complexes with the erbB-2 product in intact cells. In vitro, the bacterially expressed Shc SH2 domain is sufficient to reconstitute the high affinity Shc/erbB-2 interaction. The erbB-2 region required for Shc binding was narrowed down to the most COOH-terminal 179 residues of gp185erbB-2; within this region, phosphorylation of one or more of the erbB-2 autophosphorylation sites is required for Shc/gp185erbB-2 complex formation as well as optimal phosphorylation of Shc products by the erbB-2 kinase. Thus, Shc proteins may play a role in signal transduction by gp185erbB-2.
shc基因编码三种广泛表达的蛋白质，分子量分别为46kDa、52kDa和66kDa。在NIH3T3成纤维细胞中过表达p46shc和p52shc会诱导致瘤表型。Shc产物在酪氨酸位点被活化的表皮生长因子受体（EGFR）磷酸化，并通过其SH2结构域与EGFR发生物理结合。因此，Shc癌蛋白可能在促有丝分裂信号转导中发挥作用。在此我们报告，Shc产物也是erbB-2激酶的底物，并在完整细胞中与erbB-2产物形成复合物。在体外，细菌表达的Shc SH2结构域足以重建高亲和力的Shc/erbB-2相互作用。Shc结合所需的erbB-2区域被缩小到gp185erbB-2最COOH末端的179个残基；在该区域内，Shc/gp185erbB-2复合物形成以及erbB-2激酶对Shc产物的最佳磷酸化需要erbB-2自身磷酸化位点中的一个或多个发生磷酸化。因此，Shc蛋白可能在gp185erbB-2的信号转导中发挥作用。
