Negative regulation of phosphatidylinositol 3-kinase and Akt signalling pathway by PKC.

摘要: Although substantial studies have begun to explore the regulation of phosphatidylinositol 3-kinase/Akt cascade by different signalling pathways, whether protein kinase C (PKC) activity plays a crucial role remains as yet unclear. In this study, we found that in A549 and HEK293 cells non-selective PKC inhibitors Ro 31-8220 bisindolylmaleimide VIII, PKCbeta inhibitor LY 379196, caused Akt/PKB phosphorylation at Ser 473 increased upstream activator, integrin-linked (ILK) activity. The Akt was blocked 3-kinase wortmannin newly identified PIP(3)-dependent kinases (PDK) SB 203580. contrast stimulation inhibitors, PMA attenuated phosphorylation. We also stimulating effect on not result phosphatase inhibition, since treatment with PP2A, PP2B tyrosine (okadaic acid, FK506 sodium orthovanadate, respectively) had no effect. conclude pathway is regulated negative manner.