Ntrk1
Domain
The transmembrane domain mediates interaction with KIDINS220.
The extracellular domain mediates interaction with NGFR.
Function
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 (PubMed:1312719, PubMed:1850821, PubMed:31440771). 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.
Post-translational modifications
Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-499 mediates interaction and phosphorylation of SHC1.
N-glycosylated.
Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation (By similarity). Ubiquitination regulates the internalization of the receptor (By similarity).
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Tissue Specificity
Isoform Trka-II is primarily expressed in neuronal cells; isoform Trka-I is found in non-neuronal tissues.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Early endosome membrane
- Single-pass type I membrane protein
- Late endosome membrane
- Single-pass type I membrane protein
- Recycling endosome membrane
- Single-pass type I membrane protein
- Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation (PubMed:17724123, PubMed:26446845). Recruited to late endosomes after NGF stimulation (PubMed:17724123, PubMed:26446845). Colocalized with RAPGEF2 at late endosomes (PubMed:17724123).
Alternative names
Trk, Trka, Ntrk1, High affinity nerve growth factor receptor, Neurotrophic tyrosine kinase receptor type 1, Slow nerve growth factor receptor, p140-TrkA, Trk-A