Buday L, Downward J
Signal Transduction Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, England.
Cell. 1993 May 7;73(3):611-20. doi: 10.1016/0092-8674(93)90146-h.
Antisera against murine Son of sevenless (Sos) recognize a protein of M(r) 155,000 in rat-1 fibroblasts with specific guanine nucleotide exchange activity toward p21c-Ha-ras. Epidermal growth factor (EGF) receptor coimmunoprecipitates with Sos from EGF-stimulated, but not quiescent, cells. The SH2 and SH3 domain-containing "adapter" protein Grb2 is also found in Sos immunoprecipitates in an EGF-inducible manner. In vitro reconstitution shows that Grb2 is required for the binding of activated EGF receptor to Sos. A phosphopeptide corresponding to tyrosine 1068 of the EGF receptor blocks both the assembly of the complex and EGF stimulation of nucleotide exchange on p21ras in a permeabilized cell system. These results suggest that EGF-induced activation of nucleotide exchange on p21ras proceeds through the recruitment of cytosolic Sos to a complex with EGF receptor and Grb2 at the plasma membrane.
抗小鼠七号less之子（Sos）的抗血清在大鼠-1成纤维细胞中识别出一种分子量为155,000的蛋白质，该蛋白质对p21c-Ha-ras具有特定的鸟嘌呤核苷酸交换活性。表皮生长因子（EGF）受体在EGF刺激而非静止的细胞中与Sos共同免疫沉淀。含SH2和SH3结构域的“衔接子”蛋白Grb2也以EGF诱导的方式存在于Sos免疫沉淀复合物中。体外重组实验表明，Grb2是活化的EGF受体与Sos结合所必需的。在通透细胞系统中，对应于EGF受体酪氨酸1068的磷酸肽可阻断复合物的组装以及EGF对p21ras核苷酸交换的刺激。这些结果表明，EGF诱导的p21ras核苷酸交换激活是通过将胞质Sos募集到质膜上与EGF受体和Grb2形成的复合物来实现的。
