HUMAN SOS1 - A GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR RAS THAT BINDS TO GRB2
HUMAN SOS1 - A GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR RAS THAT BINDS TO GRB2
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DOI：
10.1126/science.8493579
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发表时间：
1993-05-28
期刊：
影响因子：
56.9
通讯作者：
BARSAGI, D
中科院分区：
文献类型：
--
作者：
CHARDIN, P;CAMONIS, JH;BARSAGI, D
分离出一个人类互补DNA，它编码一种广泛表达的蛋白质hSos 1，该蛋白质与果蝇sons of sevenless基因的产物Sos密切相关。hSos 1蛋白含有与来自酵母的Ras的鸟嘌呤核苷酸交换因子CDC 25具有显著序列相似性的区域。编码CDC25相关结构域的hSos 1片段补充了酵母中CDC25功能的丧失。该hSos1结构域在体外特异性地刺激哺乳动物Ras蛋白上的鸟嘌呤核苷酸交换。过表达全长hSos1的哺乳动物细胞具有增加的鸟嘌呤核苷酸交换活性。因此hSos 1是Ras的鸟嘌呤核苷酸交换因子。hSos 1与生长因子受体结合蛋白2（GRB 2）在体内和体外相互作用。这种相互作用是由hSos 1的羧基末端结构域和GRB 2的Src同源3（SH 3）结构域介导的。这些结果表明受体酪氨酸激酶与Ras信号的偶联是由GRB 2和hSos 1组成的分子复合物介导的。
A human complementary DNA was isolated that encodes a widely expressed protein, hSos1, that is closely related to Sos, the product of the Drosophila son of sevenless gene. The hSos1 protein contains a region of significant sequence similarity to CDC25, a guanine nucleotide exchange factor for Ras from yeast. A fragment of hSos1 encoding the CDC25-related domain complemented loss of CDC25 function in yeast. This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. Mammalian cells overexpressing full-length hSos1 had increased guanine nucleotide exchange activity. Thus hSos1 is a guanine nucleotide exchange factor for Ras. The hSos1 interacted with growth factor receptor-bound protein 2 (GRB2) in vivo and in vitro. This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1.