Tropomyosin receptor kinase C

Neurotrophic tyrosine kinase, receptor, type 3

PDB rendering based on 1wwc.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NTRK3 ; GP145-TrkC; TRKC; gp145(trkC)
External IDs OMIM: 191316 MGI: 97385 HomoloGene: 49183 ChEMBL: 5608 GeneCards: NTRK3 Gene
EC number 2.7.10.1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 4916 18213
Ensembl ENSG00000140538 ENSMUSG00000059146
UniProt Q16288 Q6VNS1
RefSeq (mRNA) NM_001007156 NM_008746
RefSeq (protein) NP_001007157 NP_032772
Location (UCSC) Chr 15:
87.86 – 88.26 Mb		 Chr 7:
78.19 – 78.58 Mb
PubMed search

Tropomyosin receptor kinase C (TrkC),[1] also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the NTRK3 gene.[2]

TrkC is the high affinity catalytic receptor for the neurotrophin NT-3 (neurotrophin-3). As such, TrkC mediates the multiple effects of this neurotrophic factor, which includes neuronal differentiation and survival.

The TrkC receptor is part of the large family of receptor tyrosine kinases. A "tyrosine kinase" is an enzyme which is capable of adding a phosphate group to the certain tyrosines on target proteins, or "substrates". A receptor tyrosine kinase is a "tyrosine kinase" which is located at the cellular membrane, and is activated by binding of a ligand via its extracellular domain. Other example of tyrosine kinase receptors include the insulin receptor, the IGF-1 receptor, the MuSK protein receptor, the Vascular Endothelial Growth Factor (or VEGF) receptor, etc. The "substrate" proteins which are phosphorylated by TrkC include PI3 kinase.

Family Members

TrkC is part of a sub-family of protein kinases which includes TrkA and TrkB. Also, there are other neurotrophic factors structurally related to NT-3: NGF (for Nerve Growth Factor), BDNF (for Brain Derived Neurotrophic Factor) and NT-4 (for Neurotrophin-4). While TrkB mediates the effects of BDNF, NT-4 and NT-3, TrkA is bound and thereby activated only by NGF. Further, TrkC binds and is activated only by NT-3.

TrkB binds BDNF and NT-4 more strongly than it binds NT-3. TrkC binds NT-3 more strongly than TrkB does.

The LNGFR

There is one other NT-3 receptor family besides the Trks (TrkC & TrkB), called the "LNGFR" (for "low affinity nerve growth factor receptor"). As opposed to TrkC, the LNGFR plays a somewhat less clear role in NT-3 biology. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that the LNGFR may signal a cell to die via apoptosis - so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.

References

  1. ↑ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 8: Atypical neurotransmitters". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. –. ISBN 9780071481274. Another common feature of neurotrophins is that they produce their physiologic effects by means of the tropomyosin receptor kinase (Trk) receptor family (also known as the tryosine receptor kinase family). ...
    Trk receptors
    All neurotrophins bind to a class of highly homologous receptor tyrosine kinases known as Trk receptors, of which three types are known: TrkA, TrkB, and TrkC. These transmembrane receptors are glycoproteins whose molecular masses range from 140 to 145 kDa. Each type of Trk receptor tends to bind specific neurotrophins: TrkA is the receptor for NGF, TrkB the receptor for BDNF and NT-4, and TrkC the receptor for NT-3.However, some overlap in the specificity of these receptors has been noted.
  2. ↑ McGregor LM, Baylin SB, Griffin CA, Hawkins AL, Nelkin BD (July 1994). "Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal assignment, and evidence for a splice variant". Genomics 22 (2): 267–72. doi:10.1006/geno.1994.1383. PMID 7806211.

Further reading

  • Lamballe F, Klein R, Barbacid M (1991). "trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3". Cell 66 (5): 967–79. doi:10.1016/0092-8674(91)90442-2. PMID 1653651. 
  • Tessarollo L, Tsoulfas P, Martin-Zanca D, et al. (1993). "trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues". Development 118 (2): 463–75. PMID 8223273. 
  • Klein R, Silos-Santiago I, Smeyne RJ, et al. (1994). "Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements". Nature 368 (6468): 249–51. doi:10.1038/368249a0. PMID 8145824. 
  • Ip NY, Stitt TN, Tapley P, et al. (1993). "Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells". Neuron 10 (2): 137–49. doi:10.1016/0896-6273(93)90306-C. PMID 7679912. 


This article is issued from Wikipedia - version of the Thursday, February 11, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.