Akt/Pkb信号通路

PATHWAYS KEY:

Since its discovery as a proto-oncogene nearly ten years ago, the serine/threonine kinase Akt, also known as protein kinase B (PKB), has become a major focus of attention because of its critical regulatory role in diverse cellular processes, including cancer progression. The Akt cascade is activated by receptor tyrosine kinases, integrins, B- and T-cell receptors, cytokine receptors, G-protein coupled receptors, and other stimuli that induce the accumulation of phosphatidylinositol 3,4,5 triphosphates, (PtdIns(3,4,5)P3), by the phosphoinositide 3-kinase (PI3K). The three Akt isoforms (Akt1, Akt2 and Akt3) thus mediate many of the downstream events regulated by PI3K. For instance, Akt is a major regulator of insulin signaling and glucose metabolism. Akt controls cell growth through its effects on the mTOR and p70 S6 kinase pathways, as well as the cell cycle and cell proliferation through its direct action on the CDK inhibitors, p21 and p27, and indirectly by affecting the levels of cyclin D1 and p53. Akt is also major mediator of cell survival by directly inhibiting different pro-apoptotic signals such as Bad and the Forkhead family of transcription factors, or indirectly by modulating two central regulators of cell death such as p53 and NF-£eB. Akt signaling in endothelial cells plays also critical roles in the regulation of vascular homeostasis and angiogenesis. These findings have turned Akt/PKB into important therapeutic target for the treatment of cancer, diabetes and stroke