Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma
Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma
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DOI：
10.1126/science.275.5298.394
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发表时间：
1997-01-17
期刊：
影响因子：
56.9
通讯作者：
Wetzker, R
中科院分区：
文献类型：
--
作者：
LopezIlasaca, M;Crespo, P;Wetzker, R
酪氨酸激酶类受体通过信号蛋白 Grb2、Sos、Ras、Raf 和 MEK 的顺序相互作用诱导丝裂原激活蛋白激酶 (MAPK) 激活。与异三聚体三磷酸鸟嘌呤结合蛋白（G 蛋白）偶联的受体通过 G（β γ）亚基刺激 MAPK，但随后的干预分子仍不清楚。 COS-7 细胞中磷酸肌醇 3-激酶 γ (PI3K γ) 的过表达以 G(β γ) 依赖性方式激活 MAPK，而 PI3K γ 的催化失活突变体的表达消除了 G(β γ) 对 MAPK 的刺激或响应毒蕈碱 (m2) G 蛋白偶联受体的刺激。从 PI3K gamma 到 MAPK 的信号传导似乎需要酪氨酸激酶、Shc、Grb2、Sos、Ras 和 Raf。这些发现表明 PI3K gamma 介导 MAPK 信号通路的 G(beta gamma) 依赖性调节。
The tyrosine kinase class of receptors induces mitogen-activated protein kinase (MAPK) activation through the sequential interaction of the signaling proteins Grb2, Sos, Ras, Raf, and MEK. Receptors coupled to heterotrimeric guanine triphosphate-binding protein (G protein) stimulate MAPK through G(beta gamma) subunits, but the subsequent intervening molecules are still poorly defined. Overexpression of phosphoinositide 3-kinase gamma (PI3K gamma) in COS-7 cells activated MAPK in a G(beta gamma)-dependent fashion, and expression of a catalytically inactive mutant of PI3K gamma abolished the stimulation of MAPK by G(beta gamma) or in response to stimulation of muscarinic (m2) G protein-coupled receptors. Signaling from PI3K gamma to MAPK appears to require a tyrosine kinase, Shc, Grb2, Sos, Ras, and Raf. These findings indicate that PI3K gamma mediates G(beta gamma)-dependent regulation of the MAPK signaling pathway.