NTRK1

Description

The NTRK1 (neurotrophic receptor tyrosine kinase 1) is a protein-coding gene located on chromosome 1.

The NTRK1 gene provides instructions for making a protein that is essential for the development and survival of nerve cells (neurons), especially those that transmit information about sensations such as pain, temperature, and touch (sensory neurons). The NTRK1 protein is found on the surface of cells, particularly sensory neurons. It acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. This process is called phosphorylation. The NTRK1 protein is turned on (activated) when another protein called nerve growth factor beta (NGFβ) attaches (binds) to it and signals the NTRK1 protein to phosphorylate itself (autophosphorylation). Then, the activated NTRK1 protein phosphorylates other proteins; this process is needed to transmit signals for cell growth and survival.

NTRK1 is a receptor tyrosine kinase essential for the development and maturation of the central and peripheral nervous systems. It plays a crucial role in regulating the proliferation, differentiation, and survival of sympathetic and nervous neurons. NTRK1 acts as a high-affinity receptor for NGF, its primary ligand, and can also be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 and has no effect on neuron survival. Upon binding of a dimeric NGF ligand, NTRK1 undergoes homodimerization, autophosphorylation, and activation. This process recruits, phosphorylates, and/or activates several downstream effectors, including SHC1, FRS2, SH2B1, SH2B2, and PLCG1, which regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2, NTRK1 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1, NTRK1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Additionally, through SHC1 and SH2B1, NTRK1 controls a Ras-PI3 kinase-AKT1 signaling cascade that also regulates survival. In the absence of ligand and activation, NTRK1 may promote cell death, making the survival of neurons dependent on trophic factors.

NTRK1 is also known as MTC, TRK, TRK1, TRKA, Trk-A, p140-TrkA.

Associated Diseases

• Hereditary sensory and autonomic neuropathy type 4
• Insensitivity to pain, congenital, with anhidrosis
• Hereditary sensory and autonomic neuropathy type 5
• Congenital insensitivity to pain with anhidrosis