Current Perspectives on Akt Akt-ivation and Akt-ions

被引:86
作者
Matheny, Ronald W., Jr.
Adamo, Martin L. [1 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA
关键词
Akt; growth; apoptosis; PROTEIN-KINASE-B; TRANSCRIPTION FACTOR FKHRL1; PLECKSTRIN-HOMOLOGY-DOMAIN; MOLECULAR-CLONING; SURVIVAL SIGNALS; PHOSPHOINOSITIDE; 3-KINASES; CELL-SURVIVAL; MICE LACKING; PHOSPHORYLATION; INSULIN;
D O I
10.3181/0904-MR-138
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The serine/threonine kinase Akt is an effector of PI3K-generated phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and is a principle mediator of growth factor-induced signal transduction. Akt is activated through phosphorylation by specific kinases, and its activity is reduced directly by phosphorylation-site-specific phosphatases. In addition, Akt activity is effectively reduced by the action of phosphatases which dephosphorylate PI(3,4,5)P3, thereby reducing the levels of the essential lipid activators of PDK1 and Akt. The functions of Akt are pleiotropic and include regulation of cellular proliferation, differentiation, protein synthesis, and survival. Akt stimulates protein synthesis through actions on mTOR/p70S6K, and promotes survival by phosphorylating and inactivating pro-apoptotic molecules such as Ask1, Bad, Bax, and Foxo3a. Furthermore, loss of Akt decreases the intracellular ATP:AMP ratio, thus establishing a role for Akt in energy regulation. Three isoforms of Akt have been identified, and although redundant functions between isoforms exist, recent investigations have enumerated unique functions for each. Therefore, targeting specific Akt isozymes in a tissue- and context-specific fashion may lead to a greater understanding of Akt-mediated processes. Exp Biol Med 234:1264-1270, 2009
引用
收藏
页码:1264 / 1270
页数:7
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