TY - JOUR
T1 - Current perspectives on akt akt-ivation and akt-ions
AU - Matheny, Ronald W.
AU - Adamo, Martin L.
PY - 2009/11/1
Y1 - 2009/11/1
N2 - 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.
AB - 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.
KW - Akt
KW - Apoptosis
KW - Growth
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U2 - 10.3181/0904-MR-138
DO - 10.3181/0904-MR-138
M3 - Short survey
C2 - 19596822
AN - SCOPUS:70350560575
VL - 234
SP - 1264
EP - 1270
JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
SN - 1535-3702
IS - 11
ER -