neurotrophic tyrosine kinase, receptor, type 3
|Locus||Chr. 15 q24-q25|
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.
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.
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.
- 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. 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. PMID 7679912.
Transmembrane receptor, tyrosine kinase: receptor tyrosine kinases (EC 188.8.131.52)
|I||EGF (HER2/neu, Her 3, Her 4)|
|II||Insulin - IGF-1|
|III||Platelet-derived growth factor|
|IV||Fibroblast growth factor (FGFR1, FGFR2, FGFR3)|
|V||VEGF receptors - Flk-1 - Flt-1|
|VII||TRK: TrkA - TrkB - TrkC|
|other||VIII: Eph (B2) - XI: Angiopoietin Receptors: Tie-1 & Tie-2 - XIV: RET - XVI: Related to receptor tyrosine kinase - XVII: MuSK|
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