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 Akt Signaling

The protein kinase B, PKB, family of proteins, also called Akt or RAC, are serine/threonine protein kinases involved in the regulation of cell survival; cell cycle progression; protein synthesis; glucose/glycogen metabolism; and a growing list of specialized cell function. Akt/PKB exists as three isoforms: AKT1 (PKB); AKT2 (PKBbeta); and AKT3 (PKBgamma). Akt/PKB is activated by phosphorylation. The principle Akt/PKB kinase is 3-phosphoinositide dependent protein kinase-1 (PDK1 (PKPK1)). Akt/PKB is dephosphorylated by protein phosphatase 2A (PP2A). Akt/PKB is maintained in an active phosphorylated state by the ligand occupation of various cytokine and growth factor receptors. Ligand-withdrawal or down-regulation of Akt/PKB activators leads to apoptosis.

Akt/PKB mediates cell survival signaling by phosphorylating several factors involved in apoptosis machinery including: caspase-9, BCL2-antagonist of cell death (BAD), forkhead in rhabdomyosarcoma-like 1 (FKHRL1); IκB kinase, IKKalpha (an NFkappaBp65 activator). Akt/PKB upregulates protein synthesis by turning off constitutively active glycogen synthase kinase-3, GSK3; and turning on mTOR (TORC1). Akt/PKB promotes cell-cycle progression by phosphorylating cyclin-dependent kinase (CDK) inhibitors; p27(Kip1) and p21(CIP1). Akt/PKB attenuates the action of the second messenger cAMP by activating the cAMP phosphodiesterases-3B (PDE-3B). Akt/PKB promotes the uptake of glucose by promoting the translocation of the GLUT-4 glucose transporter to the cell membrane.