protein_function: Receptor tyrosine kinase involved in the development andthe maturation of the central and peripheral nervous systemsthrough regulation of proliferation, differentiation and survivalof sympathetic and nervous neurons. High affinity receptor for NGFwhich is its primary ligand, it can also bind and be activated byNTF3,neurotrophin-3. However, NTF3 only supports axonal extensionthrough NTRK1 but has no effect on neuron survival. Upon dimericNGF ligand-binding, undergoes homodimerization,autophosphorylation and activation. Recruits, phosphorylatesand,or activates several downstream effectors including SHC1,FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlappingsignaling cascades driving cell survival and differentiation.Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade thatregulates cell differentiation and survival. Through PLCG1controls NF-Kappa-B activation and the transcription of genesinvolved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulatingsurvival. In absence of ligand and activation, may promote celldeath, making the survival of neurons dependent on trophicfactors.
Tropomyosin receptor kinase A(TrkA) are efficacious in attenuating skeletal pain.1 TrkA mutants were able to activate signaling cascades and were even more efficient in promoting neurite outgrowth than the wild-type receptor.2 TrkA is part of a sub-family of protein kinases which includes TrkB and TrkC. Also, there are other neurotrophic factors structurally related to NGF: BDNF(for Brain-Derived Neurotrophic Factor), NT-3(for Neurotrophin-3) and NT-4(for Neurotrophin-4). While TrkA mediates the effects of NGF, TrkB is bound and activated by BDNF, NT-4, and NT-3. Further, TrkC binds and is activated by NT-3.3 TrkA receptor was found in kehumanoconus-affected corneas, along with an increased level of repressor isoform of Sp3 transcription factor.4
