Ricketts W A, Rose D W, Shoelson S, Olefsky J M
Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093, USA.
J Biol Chem. 1996 Oct 18;271(42):26165-9. doi: 10.1074/jbc.271.42.26165.
Shc is involved in the activation of Ras in response to many growth factors. Shc contains two phosphotyrosine binding domains, an Src homology 2 (SH2) domain in the carboxyl terminus of the protein and a phosphotyrosine binding (PTB) domain in the amino terminus. Since functional roles for these two domains have not been established, we microinjected glutathione S-transferase fusion proteins of either the Shc PTB or SH2 domains into fibroblasts expressing insulin and epidermal growth factor receptors and measured their effects on DNA synthesis. We found that the Shc PTB was necessary for insulin-induced mitogenic signaling, whereas the SH2 domain was not. In contrast, for epidermal growth factor signaling, the Shc SH2 was functionally more important. These differential modes of signal transduction may be an important factor in determining the specificity of the response of a cell to external stimuli.
Shc参与响应多种生长因子时Ras的激活。Shc含有两个磷酸酪氨酸结合结构域，一个位于蛋白质羧基末端的Src同源2（SH2）结构域和一个位于氨基末端的磷酸酪氨酸结合（PTB）结构域。由于这两个结构域的功能作用尚未确定，我们将Shc PTB或SH2结构域的谷胱甘肽S-转移酶融合蛋白显微注射到表达胰岛素和表皮生长因子受体的成纤维细胞中，并测量它们对DNA合成的影响。我们发现Shc PTB是胰岛素诱导的有丝分裂信号传导所必需的，而SH2结构域则不是。相反，对于表皮生长因子信号传导，Shc SH2在功能上更重要。这些信号转导的差异模式可能是决定细胞对外部刺激反应特异性的一个重要因素。
