Phosphoinositide 3-kinase γ is a mediator of Gβγ-dependent Jun kinase activation

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 G beta gamma subunits of heterotrimeric G proteins, but the subsequent signaling reaction has been undefined. Here we demonstrate JNK activation in COS-7 cells by G beta gamma-stimulated phosphoinositide S-kinase gamma (PI3K gamma). Signal transduction from PI3K gamma to JNK can be suppressed by dominant negative mutants of Ras, Rac, and the protein kinase PAK. These results identify PI3K gamma as a mediator of G beta gamma-dependent regulation of JNK activity.