The Trk proto-oncogene encodes a tyrosine protein kinase, Trk A, also designated Trk gp140, that serves as a receptor for certain neurotrophic factors including nerve growth factor (NGF) and neurotrophin-3 (NT-3). Trk B is a tyrosine kinase gene highly related to Trk A. Trk B expression is confined to tissues within the central and peripheral nervous systems. The brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on Tyrosine of Trk B gp145, one of the receptors encoded by Trk B, although BDNF elicits a response at least two orders of magnitude greater than NT-3. Thus it appears that Trk B gp145 may represent a neurotrophic receptor for BDNF and NT-3. The third member of the Trk family of tyrosine kinases, Trk C, encodes a protein designated Trk C gp145 that is preferentially expressed in brain tissue, is equally related to Trk A and Trk B and is a functional receptor for NT-3.
Background References
1. Hempstead B L et al. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350:678-683 (1991).
2. Jing S et al. Nerve growth factor mediates signal transduction through trk homodimer receptors. Neuron 9:1067-1079 (1992).
Sequence Similarity
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Tissue Specificity
Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.
Post-translational Modification
Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1.; N-glycosylated. Isoform TrkA-I and isoform TrkA-II are N-glycosylated.; Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation. Ubiquitination regulates the internalization of the receptor (By similarity).
ICC staining TrkA in PC-12 cells (green). The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
Immunohistochemical analysis of paraffin-embedded human liver cancer tissue using anti-TrkA antibody. Counter stained with hematoxylin.
Immunohistochemical analysis of paraffin-embedded human stomach cancer tissue using anti-TrkA antibody. Counter stained with hematoxylin.
Immunohistochemical analysis of paraffin-embedded rat brain tissue using anti-TrkA antibody. Counter stained with hematoxylin.
Immunohistochemical analysis of paraffin-embedded mouse brain tissue using anti-TrkA antibody. Counter stained with hematoxylin.
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