NTRK1 gene

The NTRK1 gene (NTRK1 stands for: Neurotrophic Receptor Tyrosine Kinase 1) is a protein-coding gene located on chromosome 1q23.1. The signaling pathways associated with this gene include apoptosis pathways in synovial fibroblasts and the GPCR signaling pathway. GO (Gene Ontology) annotations associated with this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is NTRK3.

The encoded protein is a receptor tyrosine kinase that is involved in the development and maturation of the central and peripheral nervous system by regulating the proliferation, differentiation and survival of sympathetic and nervous neurons. The receptor has a high affinity for NGF, which is its primary ligand (Jing S et al. 1992; Hempstead BL et al. 1991; Barker PA et al. (1993).

The receptor tyrosine kinase can also bind to and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal expansion by NTRK1, but has no influence on the survival of neurons. After binding to the dimeric NGF ligand, homodimerization, autophosphorylation and activation occur. The NTRK1 receptor kinase recruits, phosphorylates and/or activates several downstream effectors, including SHC1, FRS2, SH2B1, SH2B2 and PLCG1, which regulate several overlapping signaling cascades that control cell survival and differentiation. It activates a GRB2-Ras-MAPK cascade via SHC1 and FRS2, which regulates cell differentiation and survival. It also controls the activation of NF-Kappa-B and the transcription of genes involved in cell survival via PLCG1. A Ras-PI3 kinase-AKT1 signaling cascade, which also regulates survival, is controlled via SHC1 and SH2B1. In the absence of ligands and activation, apoptosis can be promoted, making the survival of neurons dependent on trophic factors.

Diseases associated with NTRK1 include congenital insensitivity to pain with anhidrosis and familial medullary thyroid carcinoma.

1. Barker PA et al. (1993) Tissue-specific alternative splicing generates two isoforms of the trkA receptor. J Biol Chem 268:15150-15157.
2. Hempstead BL et al. (1991) High-affinity NGF binding requires co-expression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350:678-683.
3. Jing S et al. (1992) Nerve growth factor mediates signal transduction through trk homodimer receptors. Neuron 9:1067-1079