BackgroundInformation | Mitogen-activatedproteinkinase3(EC2.7.11.24;UniProtP21708;alsoknownasERK-1,ERT2,Extracellularsignal-regulatedkinase1,Insulin-stimulatedMAP2kinase,MAPkinase3,MAPkinaseisoformp44,MAPK3,Microtubule-associatedprotein2kinase,MNK1,p44-ERK1,p44-MAPK)isencodedbytheMapk3(alsoknownasErk1,Prkm3)gene(GeneID50689)inratspecies.ERK1(a.k.a.MAPK3)andERK2(a.k.a.MAPK1orMAPK2)arerelatedserine/threoninekinasesoftheRas-Raf-MEK-ERKsignalingpathway.ERK1/2areactivatedbyMEK1/2-catalyzedphosphorylationattheirconservedThr-Glu-Tyr(TEY)dualphosphorylationmotif,firstattheTyrresidue(human/ratERK1Tyr204/Tyr203,human/ratERK2Tyr187/Tyr183)andthenattheThrresidue(human/ratERK1Thr202/Thr201,human/ratERK2Thr185/Thr181).ERK1/2areproline-directedkinasesthatpreferentiallycatalyzethephosphorylationofPro-Xxx-Ser/Thr-Prosequencemotifinhundredsofcytoplasmicandnuclearsubstrates,includingtranscriptionfactorssuchasEts,Elk,andc-Fos.Besidesthisprimarystructurerequirement,manyERK1/2substratespossessaD-dockingsiteand/oranF-dockingsite.Avarietyofscaffoldproteins,includingKSR1/2,IQGAP1,MP1,andβ-Arrestin1/2,alsoparticipateintheregulationofERK1/2MAPkinasecascade.Ras-Raf-MEK-ERKsignalingactivityisupregulatedinaboutone-thirdofallhumancancers,andtargetedinhibitionagainstcomponentsofthissignalingpathwayrepresentsapopularanticancerstrategy. |