NT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene.[1]
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
- ↑ 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.
- Ebendal T (1992). "Function and evolution in the NGF family and its receptors.". J. Neurosci. Res. 32 (4): 461–70. doi:10.1002/jnr.490320402. PMID 1326636.
- Guiton M, Gunn-Moore FJ, Glass DJ, et al. (1995). "Naturally occurring tyrosine kinase inserts block high affinity binding of phospholipase C gamma and Shc to TrkC and neurotrophin-3 signaling.". J. Biol. Chem. 270 (35): 20384–90. doi:10.1074/jbc.270.35.20384. PMID 7657612.
- Shelton DL, Sutherland J, Gripp J, et al. (1995). "Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins.". J. Neurosci. 15 (1 Pt 2): 477–91. PMID 7823156.
- Pflug BR, Dionne C, Kaplan DR, et al. (1995). "Expression of a Trk high affinity nerve growth factor receptor in the human prostate.". Endocrinology 136 (1): 262–8. doi:10.1210/en.136.1.262. PMID 7828539.
- Lamballe F, Tapley P, Barbacid M (1993). "trkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities.". Embo J. 12 (8): 3083–94. PMC 413573. PMID 8344249.
- Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Yamamoto M, Sobue G, Yamamoto K, et al. (1997). "Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75NGFR, trkA, trkB, and trkC) in the adult human peripheral nervous system and nonneural tissues.". Neurochem. Res. 21 (8): 929–38. doi:10.1007/BF02532343. PMID 8895847.
- Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Valent A, Danglot G, Bernheim A (1997). "Mapping of the tyrosine kinase receptors trkA (NTRK1), trkB (NTRK2) and trkC(NTRK3) to human chromosomes 1q22, 9q22 and 15q25 by fluorescence in situ hybridization.". Eur. J. Hum. Genet. 5 (2): 102–4. PMID 9195161.
- Terenghi G, Mann D, Kopelman PG, Anand P (1997). "trkA and trkC expression is increased in human diabetic skin.". Neurosci. Lett. 228 (1): 33–6. doi:10.1016/S0304-3940(97)00350-9. PMID 9197281.
- Knezevich SR, McFadden DE, Tao W, et al. (1998). "A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma.". Nat. Genet. 18 (2): 184–7. doi:10.1038/ng0298-184. PMID 9462753.
- Urfer R, Tsoulfas P, O'Connell L, et al. (1998). "High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin-like domain of the Trk receptors.". J. Biol. Chem. 273 (10): 5829–40. doi:10.1074/jbc.273.10.5829. PMID 9488719.
- Hu YQ, Koo PH (1998). "Inhibition of phosphorylation of TrkB and TrkC and their signal transduction by alpha2-macroglobulin.". J. Neurochem. 71 (1): 213–20. doi:10.1046/j.1471-4159.1998.71010213.x. PMID 9648868.
- Ichaso N, Rodriguez RE, Martin-Zanca D, Gonzalez-Sarmiento R (1998). "Genomic characterization of the human trkC gene.". Oncogene 17 (14): 1871–5. doi:10.1038/sj.onc.1202100. PMID 9778053.
- Qian X, Riccio A, Zhang Y, Ginty DD (1999). "Identification and characterization of novel substrates of Trk receptors in developing neurons.". Neuron 21 (5): 1017–29. doi:10.1016/S0896-6273(00)80620-0. PMID 9856458.
- Bibel M, Hoppe E, Barde YA (1999). "Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR.". Embo J. 18 (3): 616–22. doi:10.1093/emboj/18.3.616. PMC 1171154. PMID 9927421.
- Labouyrie E, Dubus P, Groppi A, et al. (1999). "Expression of neurotrophins and their receptors in human bone marrow.". Am. J. Pathol. 154 (2): 405–15. PMC 1849993. PMID 10027399.
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| 1wwc: NT3 BINDING DOMAIN OF HUMAN TRKC RECEPTOR |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp) |
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