BackgroundInformation | Akt/PKBisaSer/ThrkinaseandamajorknowneffecterofthePI3Kinasepathway.ItisinvolvedinmultiplesignalingpathwaysthatrelatetomanyBIOLOGicalprocessesincludingglucosemetabolism,cellsurvival/apoptosis,cellcyclecontrol,angiogenesis,differentiation,andcellgrowthandproliferation.InmammalsthreeisoformsofAkt(Akt1/PKB?,Akt2/PKB?,andAkt3/PKB??)exists.Theyexhibitahighdegreeofhomology,butdifferslightlyinthelocalizationoftheirregulatoryphosphorylationsites.Akt?isthepredominantisoformthatisinmosttissuesandisthoughttohaveadominantroleingrowth,survival,embryonicdevelopment,andADIpocytedifferentiation.Akt2iscorrelatedwiththeregulationofglucosehomeostasisandisthepredominantisoformexpressedininsulin-responsivetissues.Akt3isabundantinbraintissue.EachAktisoformiscomposedofthreefunctionallydistinctregions:anN-terminalPleckstrinHomology(PH)domainthatprovidesalipid-bindingmoduletodirectAkttoPIP3atthecellmembranethatisnecessaryforitsactivation,acentralcatalyticdomaincontainingThr308,andaC-terminalhydrophobicmotifcontainingSer473.TheactivationofAktisdependentonadualregulatorymechanismthatrequiresbothitstranslocationtotheplasmamembraneanddualphosphorylationonThr308andSer473byPDK1andtheTORC2complex,respectively. |