GUANINE-NUCLEOTIDE-RELEASING FACTOR HSOS1 BINDS TO GRB2 AND LINKS RECEPTOR TYROSINE KINASES TO RAS SIGNALING
GUANINE-NUCLEOTIDE-RELEASING FACTOR HSOS1 BINDS TO GRB2 AND LINKS RECEPTOR TYROSINE KINASES TO RAS SIGNALING
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DOI：
10.1038/363085a0
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发表时间：
1993-05-06
期刊：
影响因子：
64.8
通讯作者：
SCHLESSINGER, J
中科院分区：
文献类型：
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作者：
LI, N;BATZER, A;SCHLESSINGER, J
受体酪氨酸激酶的许多作用是由蛋白Ras 1 -5介导的，包括各种下游丝氨酸/苏氨酸激酶的激活和生长和分化的刺激6 -12。人蛋白Grb 2分别通过其Src同源（SH）结构域SH 2和SH 3结合配体活化的生长因子受体和下游效应蛋白13，14，并且与其来自秀丽隐杆线虫的同源物Sem-5类似，显然形成这些受体可以控制Ras活性的高度保守途径的一部分15 -18。在这里，我们表明，SH 3结构域的Grb 2结合的羧基末端部分hSos 1，人类同源的果蝇鸟嘌呤核苷酸释放因子的Ras，这是必不可少的控制Ras活性的表皮生长因子受体和sevenless 19，20。此外，含有序列PPVPPR的合成10-氨基酸肽特异性阻断相互作用。这些结果表明Grb 2/hSos 1复合物将激活的EGF受体偶联至Ras信号传导。
MANY of the actions of receptor tyrosine kinases are mediated by the protein Ras1-5, including the activation of various downstream serine/threonine kinases and the stimulation of growth and differentiation6-12. The human protein Grb2 binds to ligand-activated growth factor receptors and downstream effector proteins through its Src-homology (SH) domains SH2 and SH3, respectively13,14, and like its homologue from Caenorhabditis elegans, Sem-5, apparently forms part of a highly conserved pathway by which these receptors can control Ras activity15-18. Here we show that the SH3 domains of Grb2 bind to the carboxy-terminal part of hSos1, the human homologue of the Drosophila guanine-nucleotide-releasing factor for Ras, which is essential for control of Ras activity by epidermal growth factor receptor and sevenless19,20. Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grb2/hSos1 complex couples activated EGF receptor to Ras signalling.