DescriptionCatalogueNumber09-203DescriptionAnti-phospho-JAK2(Tyr868)AntibodyBackgroundInformationJAK2(JanusKinase2)belongstotheemergingfamilyofnon-receptorJanustyrosinekinases,whichregulateaspectrumofcellularfunctionsdownstreamofactivatedcytokinereceptorsinthelympho-hematopoieticsystem.Immunologicalstimuli,suchasinterferonsandcytokines,inducerecruitmentofStattranscriptionfactorstocytokinereceptor-associatedJAK2.JAK2thenphosphorylatesproximalStatfactors,whichsubsequentlydimerize,translocatetothenucleusandbindtoCISelementsupstreamoftargetgenepromoterstoregulatetranscription.ThecanonicalJAK/Statpathwayisintegraltomaintaininganormalimmunesystembystimulatingproliferation,differentiation,survivalandhostresistancetopathogens.AlteringJAK/Statsignalingtoreducecytokineinducedpro-inflammatoryresponsesrepresentsanattractivetargetforanti-inflammatorytherapies.WithintheJAK2kinasedomain,thereisaregionthathasconsiderablesequencehomologytotheregulatoryregionoftheinsulinreceptor.ProductInformationFormatAffinityPurifiedPresentationPurifiedrabbitpolyclonalinbuffercontaining0.1MTris-Glycine(pH7.4,150mMNaCl)with0.05%sodiumazide.StorageandShippingInformationStorageConditionsStablefor1yearat2-8°Cfromdateofreceipt.ApplicationsApplicationAnti-phospho-JAK2(Tyr868)Antibodydetectslevelofphospho-JAK2(Tyr868)&hasbeenpublished&validatedforusein0.KeyApplicationsWesternBlottingApplicationNotesWesternBlot(SNAPID)Analysis:1:50dilutionfromapreviouslotdetectedphospho-JAK2on10µgofcelllysatesofHEK293TstimulatedwithSH2b1beta.BIOLOGicalInformationImmunogenKLH-conjugatedlinearpeptidecorrespondingtotheproteinkinase2domainofhumanphospho-JAK2.EpitopeProteinkinase2domainHostRabbitSpecificityThisantibodyrecognizestheproteinkinase2domainofJAK2.SpeciesReactivityHumanMouseSpeciesReactivityNoteDemonstratedtoreactwithhumanandmouse.Predictedtoreactwithrat,equine,opossum,bovine,chimpanzee,porcine,ape,andplatypusbasedon100%sequencehomology.AntibodyTypePolyclonalAntibodyUniProtNumberO60674UniProtSummaryFUNCTION:PlaysaroleinleptinsignalingandcontrolofbodyweightBysimilarity.Tyrosinekinaseofthenon-receptortype,involvedininterleukin-3andprobablyinterleukin-23signaltransduction.CATALYTICACTIVITY:ATP+a[protein]-L-tyrosine=ADP+a[protein]-L-tyrosinephosphate.SUBUNITSTRUCTURE:InteractswithSIRPAandSH2B1Bysimilarity.InteractswithIL23R,SKB1andSTAM2.SUBCELLULARLOCATION:Endomembranesystem;PeripheralmembraneproteinBysimilarity.Note:Whollyintracellular,possIBLymembraneassociatedBysimilarity.TISSUESPECIFICITY:Expressedinblood,bonemarrowandlymphnode.DOMAIN:Possessestwophosphotransferasedomains.ThesecondoneprobablycontainsthecatalyticdomainBysimilarity,whilethepresenceofslightdifferencessuggestadifferentrolefordomain1.PTM:Leptinpromotesphosphorylationontyrosineresidues,includingphosphorylationonTyr-813Bysimilarity.INVOLVEMENTINDISEASE:ChromosomalaberrationsinvolvingJAK2arefoundinbothchronicandacuteformsofeosinophilic,lymphoblasticandmyeloidleukemia.Translocationt(8;9)(p22;p24)withPCM1linkstheproteinkinasedomainofJAK2tothemajorportionofPCM1.Translocationt(9;12)(p24;p13)withETV6.DefectsinJAK2areacauseofsusceptibilitytoBudd-Chiarisyndrome[MIM:600880].Budd-Chiarisyndromeisaspectrumofdiseasestates,includinganatomicabnormalitiesandhypercoagulabledisorders,resultinginhepaticvenousoutflowocclusion.Clinicalmanifestationsobservedinthemajorityofpatientsincludehepatomegaly,rightupperquadrantpain,andaBDominalascites.DefectsinJAK2areassociatedwithpolycythemiavera(PV)[MIM:263300].PV,themostcommonformofprimarypolycythemia,iscausedbysomaticmutationinasinglehematopoieticstemcellleADIngtoclonalhematopoiesis.PVisamyeloproliferativedisordercharacterizedpredominantlybyerythroidhyperplasia,butalsobymyeloidleukocytosis,thrombocytosis,andsplenomegaly.FamilialcasesofPVareveryrareandusuallymanifestinelderlypatients.DefectsinJAK2genemaybeacauseofessentialthrombocythemia(ET)[MIM:187950].ETischaracterizedbyelevatedplateletlevelsduetosustainedproliferationofmegakaryocytes,andfrequentlyleadtothromboticandhaemorrhagiccomplications.DefectsinJAK2areassociatedwithfamilialmyelofibrosis[MIM:254450].Myelofibrosiswithmyeloidmetaplasiaisamyeloproliferativediseasewithannualincidenceof0.5-1.5casesper100,000individualsandageatdiagnosisaround60(anincreasedprevalenceisnotedinAshkenaziJews).Clinicalmanifestationsdependonthetypeofbloodcellaffectedandmayincludeanemia,pallor,splenomegaly,hypermetabolicstate,petechiae,ecchymosis,bleeding,lymphadenopathy,hepatomegaly,portalhypertension.DefectsinJAK2areacauseofacutemyelogenousleukemia(AML)[MIM:601626].AMLisamalignantdiseaseinwhichhematopoieticprecursorsarearrestedinanearlystageofdevelopment.SEQUENCESIMILARITIES:Belongstotheproteinkinasesuperfamily.Tyrproteinkinasefamily.JAKsubfamily.Contains1FERMdomain.Contains1proteinkinasedomain.Contains1SH2domain....MolecularWeight~125kDaObservedUniProtKB/Swiss-ProtO60674(JAK2_HUMAN)listsamassof130,674Da.PhysicochemicalInformationDimensionsMaterialsInformationMaterialsInformation