BackgroundInformation | Glycogensynthasekinase-3(GSK-3),amultifunctionalserine/threoninekinase,isakeyregulatorofnumeroussignalingpathways.TwoisoformsofGSK-3arereportedinmammals:a51kDaGSK-3aanda47kDaGSK-3b.Thesetwoisoformsexhibitabout98%homologyintheirkinasedomains,butshareonlyabout36%identityinthelast76C-terminalaminoacidresidues.GSK-3acontainsaglycine-richextensionatitsN-terminus.Aminor(~15%oftotal)splicevariantofGSK-3b,GSK-3b2,hasalsobeenidentified,whichcontainsa13-residueinsertwithinthekinasedomain.Itexhibitsreducedkinaseactivitytowardstauproteincomparedwith‘unspliced’GSK-3b.GSK-3b2islocalizedprimarilytoneuronalcellbodies,unlikeunsplicedGSK-3bthatisalsofoundinneuronalprocesses.GSK-3bplaysakeyinhibitoryroleintheWntsignalingpathway.Wntgenesencodealargefamilyofsecreted,cysteine-richproteinsthatareimportantindevelopmentandinmaintenanceofadulttissues.AbnormalitiesinWntsignalingarereportedtopromotebothhumandegenerativediseasesandcancer. |