BackgroundInformation | PathwayExplorerAntibodyMiniPack: EachPathwayExplorerAntibodyMinipackcontainsthreerelatedantibodiesaspartofasignalingcascadeoracombinationoftotalandphosphorylatedformsofkeysignalingtargets.Eachofthethreeantibodiesare30%theoriginalpacksize.FullsizeversionsofeachofthePathwayExplorerantibodiesareavailableforsaleindividuallyunderthesamecatalognumberwiththeremovalof“SP”offofeachone(e.g.05-591SPcanbeorderedas05-591).
Erk1/2: Erk(Extracellularsignal-RelatedKinase)isafamilyoftwo,highlyhomologousproteinsdenotedasErk1(p44,MAPK3)andErk2(p42,MAPK1)thatbothfunctioninthesamepathway.ThetwoproteinsareoftenreferredtocollectivelyasErk1/2orp44/p42MAPkinase.TheErkpathwayisconsideredtheclassical,canonicalMAPK(Mitogen-ActivatedProteinKinase)signalingpathway.Itisanevolutionarilyconservedpathwaythatcontrolsandisacriticalregulatorofthegrowthandsurvivalthroughthepromotionofcellproliferationandthepreventionofapoptosis.Erkisinvolvedinthecontrolofmanyfundamentalcellularprocessesincludingcellproliferation,survival,differentiation,apoptosis,motilityandmetabolism.Erkisactivatedbygrowthfactorstimulationofreceptortyrosinekinases(RTKs),GPCR,and/orintegrinstimulation.ThisactivatestheRas-Raf-MEK-Erkpathwaythatresultsinthephosphorylation/activationofErk1/2(p44/p42)ontheTxYmotif(Thr202/Tyr204andThr185/Tyr187forErk1&Erk2,respectively).
Raf: TheRafproteins(A-Raf,B-Raf,Raf-1/c-Raf)areSer/ThrkinaseswithhomologytothePKCfamily,containinganN-terminalregulatorydomainandaC-terminalcatalyticdomain.Raf(MAPKinaseKinaseKinase)isthetopkinaseinthecanonicalMAPKpathway.MembersoftheRaffamilybindtoactivatedRas.Ras,initsGTP-boundactivestate,activatesthekinaseactivityofRaf.ThisresultsinRaftranslocationtotheplasmamembraneandactivation.Onceactivated,RafthenbindstoandactivatesMEK(MAPKinaseKinase)byphosphorylatingitonthetworesiduemotif.ItisthoughtthatB-RafmightbethepredominantactivatorofMEKandthatRaf-1hasaroleinprotectionagainstapoptosis;aprocessthatdoesnotrequireeitheritskinaseactivityoritsactivationofMEK.TheregulationofalargenumberofcellularprocessesaredependentupontheactivationstateofERK,sothecontrollingofthispathwaycouldhaveprofoundeffectsonvariousdiseases.ActivationofRaf-1involvesphosphorylationofSer338/339andTyr340/341.ActivatingmutationsofB-Rafthatdisruptitsauto-inhibitionloophavebeenimplicatedinanumberofcancers,includingmelanomaandcoloncancer.
MEK1/MEK2: MAPKinase/ErkKinase(MEK),alternativelyknownasMKK,isatruedual-specificitykinase,inthatitphosphorylatestheMAPkinases(Erk1/2;p44/p42))onboththeThrandTyroftheactivationmotifTEY.Invitro,thetyrosinephosphorylationisfavored,whereasinvivobothphosphorylationeventsappeartooccursimultaneously.Thissuggeststhatanadditionalfactorispresentincellstofacilitatethereaction.MEK1andMEK2areactivatedbyphosphorylationoftwoserineresidues(Ser218/222inMEK1andSer222/226inMEK2),whicharesubstratesfortheRaffamilyofkinases.MutationofthephosphorylationsitesfromSertoAspcreatesaproteinwithconstitutivekinaseactivity,whichwhenexpressedincellsisabletocausetransformation.
*Seefullsizeversionsforcorrespondingreferences. |