通过Ras交换蛋白Sos实现Ras和Rac鸟苷三磷酸酶的偶联。

Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos.

作者信息

Nimnual A S, Yatsula B A, Bar-Sagi D

机构信息

Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.

出版信息

Science. 1998 Jan 23;279(5350):560-3. doi: 10.1126/science.279.5350.560.

DOI:10.1126/science.279.5350.560

PMID:9438849

Abstract

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.

摘要

七无之子（Sos）蛋白通过催化Ras上的二磷酸鸟苷与三磷酸鸟苷的交换，控制受体介导的Ras激活。Sos的NH2末端区域包含一个与pleckstrin同源（PH）结构域串联的Dbl同源（DH）结构域。在COS-1细胞中，Sos的DH结构域在体外和体内均刺激Rac上的鸟嘌呤核苷酸交换，但不刺激Cdc42。Sos的串联DH-PH结构域（DH-PH-Sos）在Rac激活方面存在缺陷，但当它与激活的Ras共表达时恢复了Rac刺激活性。Ras介导的DH-PH-Sos激活不需要丝裂原活化蛋白激酶的激活，但它依赖于磷脂酰肌醇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。