Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos
Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos
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DOI：
10.1126/science.279.5350.560
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发表时间：
1998-01-23
期刊：
影响因子：
56.9
通讯作者：
Bar-Sagi, D
中科院分区：
文献类型：
--
作者：
Nimnual, AS;Yatsula, BA;Bar-Sagi, D
Sos蛋白通过催化Ras上二磷酸鸟苷与三磷酸鸟苷的交换来控制受体介导的Ras活化。Sos的NH 2-末端区域含有与普列克底物蛋白同源（PH）结构域串联的Dbl同源（DH）结构域。在COS-1细胞中，DH结构域的Sos刺激鸟嘌呤核苷酸交换的Rac，但不Cdc 42在体外和体内。Sos的串联DH-PH结构域（DH-PH-Sos）不能激活Rac，但当它与激活的Ras共表达时，可以恢复Rac的激活活性。Ras介导的DH-PH-Sos的激活不需要丝裂原活化蛋白激酶的激活，但依赖于磷酸肌醇3-激酶的激活。这些结果揭示了Ras和Rac信号通路偶联的潜在机制。
The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras, Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.