EPIDERMAL GROWTH-FACTOR REGULATES P21(RAS) THROUGH THE FORMATION OF A COMPLEX OF RECEPTOR, GRB2 ADAPTER PROTEIN, AND SOS NUCLEOTIDE EXCHANGE FACTOR
EPIDERMAL GROWTH-FACTOR REGULATES P21(RAS) THROUGH THE FORMATION OF A COMPLEX OF RECEPTOR, GRB2 ADAPTER PROTEIN, AND SOS NUCLEOTIDE EXCHANGE FACTOR
复制标题
DOI：
10.1016/0092-8674(93)90146-h
复制
发表时间：
1993-05-07
期刊：
影响因子：
64.5
通讯作者：
DOWNWARD, J
中科院分区：
文献类型：
--
作者：
BUDAY, L;DOWNWARD, J
抗小鼠Son of sevenless（Sos）的抗血清识别大鼠-1成纤维细胞中的M（r）155，000蛋白，该蛋白对p21 c-Ha-ras具有特异性鸟嘌呤核苷酸交换活性。表皮生长因子（EGF）受体与来自EGF刺激的Sos共免疫沉淀，但不与静止细胞共免疫沉淀。含有SH 2和SH 3结构域的“适配器"蛋白Grb 2也以EGF诱导的方式在Sos免疫沉淀物中发现。体外重组表明，Grb 2是激活的EGF受体与Sos结合所必需的。对应于EGF受体的酪氨酸1068的磷酸肽阻断复合物的组装和透化细胞系统中p21 ras上核苷酸交换的EGF刺激。这些结果表明，EGF诱导的激活p21 ras上的核苷酸交换的收益通过招聘的胞质Sos与EGF受体和Grb 2在质膜的复合物。
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.