Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.

• GO:0007190 : activation of adenylate cyclase activity
• GO:0000186 : activation of MAPKK activity
• GO:0007202 : activation of phospholipase C activity
• GO:0060385 : axonogenesis involved in innervation
• GO:0030183 : B cell differentiation
• GO:0071363 : cellular response to growth factor stimulus
• GO:0010623 : developmental programmed cell death
• GO:0042490 : mechanoreceptor differentiation
• GO:0008285 : negative regulation of cell proliferation
• GO:0043524 : negative regulation of neuron apoptotic process
• GO:0048015 : phosphatidylinositol-mediated signaling
• GO:0045766 : positive regulation of angiogenesis
• GO:0070374 : positive regulation of ERK1 and ERK2 cascade
• GO:0010976 : positive regulation of neuron projection development
• GO:0051092 : positive regulation of NF-kappaB transcription factor activity
• GO:0043068 : positive regulation of programmed cell death
• GO:0032320 : positive regulation of Ras GTPase activity
• GO:0046579 : positive regulation of Ras protein signal transduction
• GO:0046777 : protein autophosphorylation
• GO:0007265 : Ras protein signal transduction
• GO:0048485 : sympathetic nervous system development

Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/

• OMIM:191315 : Insensitivity to pain, congenital, with anhidrosis (OMIM:256800 )
• OMIM:191315 : Medullary thyroid carcinoma, familial (OMIM:155240 )

Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/