| UniProtSummary | FUNCTION:Constitutivelyactiveproteinkinasethatactsasanegativeregulatorinthehormonalcontrolofglucosehomeostasis,Wntsignalingandregulationoftransctiptionfactorsandmicrotubules,byphosphorylatingandinactivatingglycogensynthase(GYS1orGYS2),CTNNB1/beta-catenin,APCandAXIN1.Requiresprimedphosphorylationofthemajorityofitssubstrates.ContributestoinsulinregulationofglycogensynthesisbyphosphorylatingandinhibitingGYS1activityandhenceglycogensynthesis.Regulatesglycogenmetabolisminliver,butnotinmuscle.Mayalsomediatethedevelopmentofinsulinresistancebyregulatingactivationoftranscriptionfactors.InWntsignaling,regulatesthelevelandtranscriptionalactivityofnuclearCTNNB1/beta-catenin.Facilitatesamyloidprecursorprotein(APP)processingandthegenerationofAPP-derivedamyloidplaquesfoundinAlzheimerdisease.Maybeinvolvedintheregulationofreplicationinpancreaticbeta-cells.Isnecessaryfortheestablishmentofneuronalpolarityandaxonoutgrowth.
  CATALYTICACTIVITY:ATP+[tauprotein]=ADP+[tauprotein]phosphate.
  ATP+aprotein=ADP+aphosphoprotein.
  ENZYMEREGULATION:ActivatedbyphosphorylationatTyr-279.Inresponsetoinsulin,inhibitedbyphosphorylationatSer-21byPKB/AKT1;phosphorylationatthissitecausesaconformationalchange,preventingaccessofsubstratestotheactivesite.Inhibitedbylithium.
  SUBUNITSTRUCTURE:Monomer.InteractswithARRB2(Bysimilarity).InteractswithAXIN1andCTNNB1/beta-catenin.
  PTM:PhosphorylatedbyAKT1atSer-21:uponinsulin-mediatedsignaling,theactivatedPKB/AKT1proteinkinasephosphorylatesanddesactivatesGSK3A,resultinginthedephosphorylationandactivationofGYS1.ActivatedbyphosphorylationatTyr-279.
  MISCELLANEOUS:HigherexpressionandactivityofGSK3Aarefoundintheskeletalmuscle(vastuslateralis)ofpatientswithtype2diabetes(Ref.5).SeveralpotentGSK3(GSK3AandGSK3B)inhibitorshavebeenidentifiedandcharacterizedinpreclinicalmodelsfortreatmentsoftype2diabetes(Ref.17).
  SEQUENCESIMILARITIES:Belongstotheproteinkinasesuperfamily.CMGCSer/Thrproteinkinasefamily.GSK-3subfamily.
  Contains1proteinkinasedomain. |