Lopez-Ilasaca M, Gutkind J S, Wetzker R
Max Planck Research Unit "Molecular Cell Biology," Medical Faculty, University of Jena, 07747 Jena, Germany.
J Biol Chem. 1998 Jan 30;273(5):2505-8. doi: 10.1074/jbc.273.5.2505.
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.
Jun激酶（JNK）参与哺乳动物细胞的应激反应。应激因素以及酪氨酸激酶和G蛋白偶联受体的激动剂均可诱导JNK的激活。G蛋白依赖性受体通过异源三聚体G蛋白的Gβγ亚基刺激JNK，但随后的信号反应尚不清楚。在此，我们证明了Gβγ刺激的磷酸肌醇3激酶γ（PI3Kγ）可在COS-7细胞中激活JNK。从PI3Kγ到JNK的信号转导可被Ras、Rac和蛋白激酶PAK的显性负性突变体所抑制。这些结果表明PI3Kγ是Gβγ依赖性JNK活性调节的介质。
