Langlois J, Leitner W, Medh J, Sasaoka T, Olefsky J M, Draznin B
Medical Research Service, Veterans Affairs Medical Center, 92093, San Diego, California, USA.
Endocrine. 1995 Jul;3(7):475-9. doi: 10.1007/BF02738820.
Insulin increases activity of the guanine nucleotide exchange factor (GEF) in Rat-1 fibroblasts transfected with human insulin receptors (HIRc cells), thereby promoting formation of the active form of p21Ras (p21Ras•GTP). In order to identify the upstream molecules mediating this aspect of insulin action, we selectively removed some of these molecules by immunoprecipitation and examined GEF activity in the post-immunoprecipitation lysated of the insulin-treated HIRc cells. The removal of Shc or Grb-2 depleted GEF activity from the cell lysates, whereas immuno-precipitation of the insulin receptors, IRS-1, PLCγ and GAP, were without effect. In summary, the current data demonstrate that a majority of cellular Ras GEF activity after insulin stimulation is associated with Shc and involves interactions among Shc, Grb-2 and Sos.
胰岛素可增强转染了人胰岛素受体的大鼠-1成纤维细胞（HIRc细胞）中鸟嘌呤核苷酸交换因子（GEF）的活性，从而促进活性形式的p21Ras（p21Ras•GTP）的形成。为了鉴定介导胰岛素这一作用方面的上游分子，我们通过免疫沉淀选择性去除了其中一些分子，并检测了胰岛素处理的HIRc细胞免疫沉淀后裂解物中的GEF活性。去除Shc或Grb-2可使细胞裂解物中的GEF活性降低，而胰岛素受体、IRS-1、PLCγ和GAP的免疫沉淀则没有影响。总之，目前的数据表明，胰岛素刺激后细胞中大部分Ras GEF活性与Shc相关，并且涉及Shc、Grb-2和Sos之间的相互作用。
