BackgroundInformation | TrkA,apparentmolecularweight140kDa,isahighaffinitynervegrowthfactor(NGF).TheTrkproto-oncogenefamilycontainsfourmembers,TrkA,TrkB,TrkC,andTrkE,whicharevariablyexpressedthroughoutthecentralandperipheralnervoussystems.TrkAbindstonervegrowthfactor(NGF)andautophosphorylatesontyrosineresidues(Tyr490,Tyr674,Tyr675,Tyr751andTyr785)toactivatemultipledownstreameffectorproteins.PhosphorylationatTyr490isrequiredforShcassociationandsubsequentactivationoftheRas-MAPkinase-signalingcascade,whichleadstoactivationofElk-1-dependentgenetranscriptionandneuritegrowth.PhosphorylationsatTyr674andTyr675liewithinthecatalyticdomainofTrkAtyrosinekinaseandreflectTrkkinaseactivity.Additionally,phosphorylationatTyr751isrequiredforPI3-kinaseassociationandactivationoftheAktsignalingcascade. |