Type:Protein
SpeciesReactivity:R
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;AllTrkA,theproductoftheproto-oncogenetrk,isamemberoftheneurotrophictyrosinekinasereceptorfamilythathasthreemembers.TrkA,TrkBandTrkCpreferentiallybindNGF,NT-4andBDNF,andNT-3,respectively.AllTrkfamilyproteinsshareaconservedcomplexsubdomainorganizationconsistingofasignalpeptide,twocysteine-richdomains,aclusterofthreeleucine-richmotifs,andtwoimmunoglobulin-likedomainsintheextracellularregion,aswellasanintracellularregionthatcontainsthetyrosinekinasedomain.TwodistinctratTrkAisoforms(TrkA-IandTrk-A-II)thatdifferbya6-aminoacidinsertionintheirextracellulardomainhavebeenidentified.ThelongerTrkAisoformistheonlyisoformexpressedwithinneuronaltissueswhereastheshorterTrkA-Iisexpressedmainlyinnon-neuronaltissues.NGFbindstoTrkAwithlowaffinityandactivatesitscytoplasmickinase,initiatingasignalingcascadethatmediatesneuronalsurvivalanddifferentiation.HigheraffinitybindingofNGFrequiresthecoexpressionofTrkAwiththep75NGFreceptor(NGFR),amemberofthetumornecrosisfactorreceptorsuperfamily.NGFRbindsallneurotrophinswithlowaffinityandmodulatesTrkactivityaswellasaltersthespecificityofTrkreceptorsfortheirligands.NGFRcanalsomediatecelldeathwhenexpressedindependentofTrk(Esposito,D.etal.,2001,J.Biol.Chem.276:32687;Sofroniew,M.V.etal.,2001,Annu.Rev.Neurosci.24:1217).
