title: Phosphoinositide 3-kinase gamma is a mediator of Gbetagamma-dependent Jun kinase activation.
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.
authors.affiliation: Max Planck Research Unit "Molecular Cell Biology," Medical Faculty, University of Jena, 07747 Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Ilasaca
authors.forename: J S
authors.initials: JS
authors.lastname: Gutkind
authors.forename: R
authors.initials: R
authors.lastname: Wetzker
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines / Q000494:pharmacology; D015398:Signal Transduction; D000077191:Wortmannin; D020744:rac GTP-Binding Proteins; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000730:Androstadienes; D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019870:1-Phosphatidylinositol 4-Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D018631:ras Proteins; D000077191:Wortmannin