Abstract
Jun kinases (JNK) are involved in the stress response of mammalian cells. Stimulation of JNK can be induced by stress factors and by agonists of tyrosine kinase and G protein-coupled receptors. G protein-dependent receptors stimulate JNK via Gbetagamma subunits of heterotrimeric G proteins, but the subsequent signaling reaction has been undefined. Here we demonstrate JNK activation in COS-7 cells by Gbetagamma-stimulated phosphoinositide 3-kinase gamma (PI3Kgamma). Signal transduction from PI3Kgamma to JNK can be suppressed by dominant negative mutants of Ras, Rac, and the protein kinase PAK. These results identify PI3Kgamma as a mediator of Gbetagamma-dependent regulation of JNK activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Phosphatidylinositol 4-Kinase / metabolism*
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Androstadienes / pharmacology
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Animals
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Chromones / pharmacology
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Enzyme Activation / drug effects
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases*
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Morpholines / pharmacology
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Signal Transduction
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Wortmannin
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rac GTP-Binding Proteins
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Androstadienes
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Chromones
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Morpholines
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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1-Phosphatidylinositol 4-Kinase
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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GTP-Binding Proteins
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rac GTP-Binding Proteins
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ras Proteins
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Wortmannin