UniProtSummary | FUNCTION:Tyrosine-proteinkinasethatactsasacell-surfacereceptorforPDGFA,PDGFBandPDGFCandplaysanessentialroleintheregulationofembryonicdevelopment,cellproliferation,survivalandchemotaxis.Dependingonthecontext,promotesorinhibitscellproliferationandcellmigration.Playsanimportantroleinthedifferentiationofbonemarrow-derivedmesenchymalstemcells.Requiredfornormalskeletondevelopmentandcephalicclosureduringembryonicdevelopment.Requiredfornormaldevelopmentofthemucosaliningthegastrointestinaltract,andforrecruitmentofmesenchymalcellsandnormaldevelopmentofintestinalvilli.Playsaroleincellmigrationandchemotaxisinwoundhealing.Playsaroleinplateletactivation,secretionofagoNISTsfromplateletgranules,andinthrombin-inducedplateletaggregation.Bindingofitscognateligands-homodimericPDGFA,homodimericPDGFB,heterodimersformedbyPDGFAandPDGFBorhomodimericPDGFC-leadstotheactivationofseveralsignalingcascades;theresponsedependsonthenatureoftheboundligandandismodulatedbytheformationofheterodimersbetweenPDGFRAandPDGFRB.PhosphorylatesPIK3R1,PLCG1,andPTPN11.ActivationofPLCG1leadstotheproductionofthecellularsignalingmoleculesdiacylglycerolandinositol-1,4,5-trisphosphate,mobilizationofcytosolicCa2+andtheactivationofproteinkinaseC.PhosphorylatesPIK3R1,theregulatorysubunitofphosphatidylinositol3-kinase,andtherebymediatesactivationoftheAKT1signalingpathway.MediatesactivationofHRASandoftheMAPkinasesMAPK1/ERK2and/orMAPK3/ERK1.PromotesactivationofSTATfamilymembersSTAT1,STAT3andSTAT5Aand/orSTAT5B.Receptorsignalingisdown-regulatedbyproteinphosphatasesthatdephosphorylatethereceptoranditsdown-streameffectors,andbyrapidinternalizationoftheactivatedreceptor.
CATALYTICACTIVITY:ATP+a[protein]-L-tyrosine=ADP+a[protein]-L-tyrosinephosphate.
ENZYMEREGULATION:Presentinaninactiveconformationintheabsenceofboundligand.BindingofPDGFAand/orPDGFBleadstodimerizationandactivationbyautophosphorylationontyrosineresidues.Inhibitedbyimatinib,nilotinibandsorafenib.
SUBUNITSTRUCTURE:InteractswithhomodimericPDGFA,PDGFBandPDGFC,andwithheterodimersformedbyPDGFAandPDGFB.Monomerintheabsenceofboundligand.InteractionwithdimericPDGFA,PDGFBand/orPDGFCleadstoreceptordimerization,wherebothPDGFRAhomodimersandheterodimerswithPDGFRBareobserved.Interacts(tyrosinephosphorylated)withSHB(viaSH2domain)(Bysimilarity).Interacts(tyrosinephosphorylated)withSHF(viaSH2domain).Interacts(tyrosinephosphorylated)withSRC(viaSH2domain).Interacts(tyrosinephosphorylated)withPIK3R1.Interacts(tyrosinephosphorylated)withPLCG1(viaSH2domain).Interacts(tyrosinephosphorylated)withCRK,GRB2andGRB7.SUBCELLULARLOCATION:Cellmembrane;Single-passtypeImembraneprotein.Note:Theactivatedreceptorisrapidlyinternalizedanddegraded.
TISSUESPECIFICITY:Detectedinplatelets(atproteinlevel).Widelyexpressed.Detectedinbrain,fibroblasts,smoothmuscle,heart,andembryo.Expressedinprimaryandmetastaticcolontumorsandinnormalcolontissue.
PTM:N-glycosylated.
Ubiquitinated,leADIngtoitsdegradationProbable.
Autophosphorylatedontyrosineresiduesuponligandbinding.Autophosphorylationoccursintrans,i.e.onesubunitofthedimericreceptorphosphorylatestyrosineresiduesontheothersubunit.PhosphorylationatTyr-731andTyr-742isimportantforinteractionwithPIK3R1.PhosphorylationatTyr-720andTyr-754isimportantforinteractionwithPTPN11.PhosphorylationatTyr-762isimportantforinteractionwithCRK.PhosphorylationatTyr-572andTyr-574isimportantforinteractionwithSRCandSRCfamilymembers.PhosphorylationatTyr-988andTyr-1018isimportantforinteractionwithPLCG1.
INVOLVEMENTINDISEASE:Note=AchromosomalaberrationinvolvingPDGFRAisfoundinsomecasesofhypereosinophilicsyndrome.Interstitialchromosomaldeletiondel4(q12q12)causesthefusionofFIP1L1andPDGFRA(FIP1L1-PDGFRA).Mutationsthatcauseoverexpressionand/orconstitutiveactivationofPDGFRAmaybeacauseofhypereosinophilicsyndrome.
DefectsinPDGFRAareacauseofgastrointestinalstromaltumor(GIST)[MIM:606764].Note=MutationsthatcauseconstitutiveactivationofPDGFRAmaybeacauseofgastrointestinalstromaltumor(GIST).
SEQUENCESIMILARITIES:Belongstotheproteinkinasesuperfamily.Tyrproteinkinasefamily.CSF-1/PDGFreceptorsubfamily.
Contains5Ig-likeC2-type(immunoglobulin-like)domains.
Contains1proteinkinasedomain.
SEQUENCECAUTION:ThesequenceAAP69563.1differsfromthatshown.Reason:Erroneousinitiation.TranslationN-terminallyshortened. |