BackgroundInformation | Akt/PKBisaSer/ThrkinaseandamajorknowneffecterofthePI3Kinasepathway.ItisinvolvedinmultiplesignalingpathwaysthatrelatetomanyBIOLOGicalprocessesincludingmetabolism,apoptosis,cellcyclecontrol,angiogenesis,differentiation,andcellgrowthandproliferation.Inmammals,threeisoformsofAkt(Akt1/PKCα,Akt2/PKBβ,andAkt3/PKBγ)exists.Theyexhibitahighdegreeofhomology,butdifferslightlyinthelocalizationoftheirregulatoryphosphorylationsites.Akt1isthepredominantisoformthatisinmosttissuesandisthoughttohaveadominantroleingrowth,survival,embryonicdevelopment,andADIpocytedifferentiation.Akt2iscorrelatedwiththeregulationofglucosehomeostasisandisthepredominantisoformexpressedininsulin-responsivetissues.Akt3isabundantinbraintissue.EachAktisoformiscomposedofthreefunctionallydistinctregions:anN-terminalPleckstrinHomology(PH)domainthatprovidesalipid-bindingmodule,acentralcatalyticdomaincontainingThr308,andaC-terminalhydrophobicmotifcontainingSer473.TheactivationofAKTisdependentonadualregulatorymechanismthatrequiresbothitstranslocationtotheplasmamembraneanddualphosphorylationonThr308andSer473byPDK1andtheTORC2complex,respectively. |