TrkB

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neurotrophic tyrosine kinase, receptor, type 2
Symbol(s):	NTRK2
Locus:	9 q22.1
EC number	2.7.1.112
EntrezGene	4915
OMIM	600456
RefSeq	NM_001007097
UniProt	Q16620

Function

TrkB is the high affinity receptor for several "neurotrophins", which are small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: Brain Derived Neurotrophic Factor, or "BDNF", NT-4 (neurotrophin-4), and NT-3 (neurotrophin-3). As such, TrkB mediates the multiple effects of these neurotrophic factors, which includes neuronal differentiation and survival.

The TrkB 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 TrkB include PI 3 kinase.

Family Members

TrkB is part of a sub-family of protein kinases which includes TrkA and TrkC. Also, there are other neurotrophic factors structurally related to BDNF: NGF (for Nerve Growth Factor), NT-3 (for Neurotrophin-3) 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 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 BDNF receptor besides TrkB, called the "LNGFR" (for "low affinity nerve growth factor receptor"). As opposed to TrkB, the LNGFR plays a somewhat less clear role in BDNF 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.

Citations

[1] The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain.

[2] trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor

[3] TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor