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neurotrophic tyrosine kinase, receptor, type 3
Symbol(s): NTRK3
Locus: 15 q24 -q25
EC number 2.7.1.112
EntrezGene 4916
OMIM 191316
RefSeq NM_001007156
UniProt Q16288

TrkC is the high affinity 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 kianse 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 IGF1 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 MembersEdit

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 LNGFREdit

There is one other NT-3 receptor besides TrkC, 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.

CitationsEdit

[1] trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3

[2] trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues

[3] Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements.

[4] Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells

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