Phosphatidylinositol 3-Kinase Is an Early Intermediate in the Gβγ-mediated Mitogen-activated Protein Kinase Signaling Pathway

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作者：

BE Hawes，LM Luttrell，T Van Biesen，RJ Lefkowitz

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摘要：

The beta gamma-subunit of Gi mediates mitogen-activated protein (MAP) kinase activation through a signaling pathway involving Shc tyrosine phosphorylation, subsequent formation of a multiprotein complex including Shc, Grb2, and Sos, and sequential activation of Ras, Raf, and MEK. The mechanism by which G beta gamma mediates tyrosine phosphorylation of Shc, however, is unclear. This study assesses the role of phosphatidylinositol 3-kinase (PI-3K) in G beta gamma-mediated MAP kinase activation. We show that Gi-coupled receptor- and G beta gamma-stimulated MAP kinase activation is attenuated by the PI-3K inhibitors wortmannin and LY294002 or by over expression of a dominant negative mutant of the p85 subunit of PI-3K. Wortmannin and LY294002 also inhibit Gi-coupled receptor-stimulated Ras activation. The PI-3K inhibitors do not affect MAP kinase activation stimulated by over-expression of Sos, a constitutively active mutant of Ras, or a constitutively active mutant of MEK. These results demonstrate that PI-3K activity is required in the G beta gamma-mediated MAP kinase signaling pathway at a point upstream of Sos and Ras activation.

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关键词：

Monstrilloida Thaumaleus Monstrilla Copepoda South Atlantic Brazilian Coast

DOI：

10.1074/jbc.271.21.12133

被引量：

1412

年份：

1996