Tropomyosin receptor kinase B (TrkB), also known as Tryosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF).
Tropomyosin receptor kinase B is the high affinity catalytic 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: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3). As such, TrkB mediates the multiple effects of these neurotrophic factors, which includes neuronal differentiation and survival. Research has shown that activation of the TrkB receptor can lead to down regulation of the KCC2 chloride transporter in cells of the CNS. 
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 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 to the receptor's extracellular domain. Other examples of tyrosine kinase receptors include the insulin receptor, the IGF1 receptor, the MuSK protein receptor, the Vascular Endothelial Growth Factor (or VEGF) receptor, etc.
Currently, there are three TrkB isoforms in the mammalian CNS. The full-length isoform (TK+) is a typical tyrosine kinase receptor, and transduces the BDNF signal via Ras-ERK, PI3K, and PLCγ. In contrast, two truncated isoforms (TK-: T1 and T2) possess the same extracellular domain, transmembrane domain, and first 12 intracellular amino acid sequences as TK+. However, the C-terminal sequences are the isoform-specific (11 and 9 amino acids, respectively). T1 has the original signaling cascade that is involved in the regulation of cell morphology and calcium influx.
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.
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.
^ abcdMalenka 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. –. ISBN9780071481274. 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.
^Nakagawara A, Liu XG, Ikegaki N, White PS, Yamashiro DJ, Nycum LM, Biegel JA, Brodeur GM (January 1995). "Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2)". Genomics25 (2): 538–46. doi:10.1016/0888-7543(95)80055-Q. PMID7789988.
^Haniu M, Montestruque S, Bures EJ, Talvenheimo J, Toso R, Lewis-Sandy S, Welcher AA, Rohde MF (October 1997). "Interactions between brain-derived neurotrophic factor and the TRKB receptor. Identification of two ligand binding domains in soluble TRKB by affinity separation and chemical cross-linking". J. Biol. Chem.272 (40): 25296–303. doi:10.1074/jbc.272.40.25296. PMID9312147.
^Naylor RL, Robertson AG, Allen SJ, Sessions RB, Clarke AR, Mason GG, Burston JJ, Tyler SJ, Wilcock GK, Dawbarn D (March 2002). "A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4". Biochem. Biophys. Res. Commun.291 (3): 501–7. doi:10.1006/bbrc.2002.6468. PMID11855816.
^ abcSuzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S (June 2002). "Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor". Biochem. Biophys. Res. Commun.294 (5): 1087–92. doi:10.1016/S0006-291X(02)00606-X. PMID12074588.
^Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM (April 1999). "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem.274 (14): 9861–70. doi:10.1074/jbc.274.14.9861. PMID10092678.
^Geetha T, Wooten MW (February 2003). "Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling". J. Biol. Chem.278 (7): 4730–9. doi:10.1074/jbc.M208468200. PMID12471037.
^Nakamura T, Muraoka S, Sanokawa R, Mori N (March 1998). "N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their differential regional expression in the brain and roles in neurotrophin and Src signaling". J. Biol. Chem.273 (12): 6960–7. doi:10.1074/jbc.273.12.6960. PMID9507002.
^Liu X, Chan CB, Jang SW, Pradoldej S, Huang J, He K, Phun LH, France S, Xiao G, Jia Y, Luo HR, Ye K (November 2010). "A Synthetic 7,8-Dihydroxyflavone Derivative Promotes Neurogenesis and Exhibits Potent Antidepressant Effect". J Med Chem53: 8274. doi:10.1021/jm101206p. PMID21073191.
Klein R, Conway D, Parada LF, Barbacid M (May 1990). "The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain". Cell61 (4): 647–56. doi:10.1016/0092-8674(90)90476-U. PMID2160854.
Squinto SP, Stitt TN, Aldrich TH, Davis S, Bianco SM, Radziejewski C, Glass DJ, Masiakowski P, Furth ME, Valenzuela DM (May 1991). "trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor". Cell65 (5): 885–93. doi:10.1016/0092-8674(91)90395-F. PMID1710174.
Rose CR, Blum R, Pichler B, Lepier A, Kafitz KW, Konnerth A (November 2003). "Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells". Nature426 (6962): 74–8. doi:10.1038/nature01983. PMID14603320.
Ohira K, Kumanogoh H, Sahara Y, Homma KJ, Hirai H, Nakamura S, Hayashi M (February 2005). "A truncated tropomyosin-related kinase B receptor, T1, regulates glial cell morphology via Rho GDP dissociation inhibitor 1". J. Neurosci.25 (6): 1343–53. doi:10.1523/JNEUROSCI.4436-04.2005. PMID15703388.
Yamada K, Nabeshima T (2004). "Brain-derived neurotrophic factor/TrkB signaling in memory processes.". J. Pharmacol. Sci.91 (4): 267–70. doi:10.1254/jphs.91.267. PMID12719654.
Soppet D, Escandon E, Maragos J, Middlemas DS, Reid SW, Blair J, Burton LE, Stanton BR, Kaplan DR, Hunter T, Nikolics K, Parada LF (1991). "The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor.". Cell65 (5): 895–903. doi:10.1016/0092-8674(91)90396-G. PMID1645620.
Squinto SP, Stitt TN, Aldrich TH, Davis S, Bianco SM, Radziejewski C, Glass DJ, Masiakowski P, Furth ME, Valenzuela DM (1991). "trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor.". Cell65 (5): 885–93. doi:10.1016/0092-8674(91)90395-F. PMID1710174.
Haniu M, Talvenheimo J, Le J, Katta V, Welcher A, Rohde MF (1995). "Extracellular domain of neurotrophin receptor trkB: disulfide structure, N-glycosylation sites, and ligand binding.". Arch. Biochem. Biophys.322 (1): 256–64. doi:10.1006/abbi.1995.1460. PMID7574684.
Ip NY, Stitt TN, Tapley P, Klein R, Glass DJ, Fandl J, Greene LA, Barbacid M, Yancopoulos GD (1993). "Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells.". Neuron10 (2): 137–49. doi:10.1016/0896-6273(93)90306-C. PMID7679912.
Slaugenhaupt SA, Blumenfeld A, Liebert CB, Mull J, Lucente DE, Monahan M, Breakefield XO, Maayan C, Parada L, Axelrod FB (1995). "The human gene for neurotrophic tyrosine kinase receptor type 2 (NTRK2) is located on chromosome 9 but is not the familial dysautonomia gene.". Genomics25 (3): 730–2. doi:10.1016/0888-7543(95)80019-I. PMID7759111.
Shelton DL, Sutherland J, Gripp J, Camerato T, Armanini MP, Phillips HS, Carroll K, Spencer SD, Levinson AD (1995). "Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins.". J. Neurosci.15 (1 Pt 2): 477–91. PMID7823156.
Allen SJ, Dawbarn D, Eckford SD, Wilcock GK, Ashcroft M, Colebrook SM, Feeney R, MacGowan SH (1994). "Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain.". Neuroscience60 (3): 825–34. doi:10.1016/0306-4522(94)90507-X. PMID7936202.
Rydén M, Ibáñez CF (1996). "Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC.". J. Biol. Chem.271 (10): 5623–7. doi:10.1074/jbc.271.10.5623. PMID8621424.
Yamamoto M, Sobue G, Yamamoto K, Terao S, Mitsuma T (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. PMID8895847.
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. PMID9195161.
Haniu M, Montestruque S, Bures EJ, Talvenheimo J, Toso R, Lewis-Sandy S, Welcher AA, Rohde MF (1997). "Interactions between brain-derived neurotrophic factor and the TRKB receptor. Identification of two ligand binding domains in soluble TRKB by affinity separation and chemical cross-linking.". J. Biol. Chem.272 (40): 25296–303. doi:10.1074/jbc.272.40.25296. PMID9312147.
Nakamura T, Muraoka S, Sanokawa R, Mori N (1998). "N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their differential regional expression in the brain and roles in neurotrophin and Src signaling.". J. Biol. Chem.273 (12): 6960–7. doi:10.1074/jbc.273.12.6960. PMID9507002.
Hackett SF, Friedman Z, Freund J, Schoenfeld C, Curtis R, DiStefano PS, Campochiaro PA (1998). "A splice variant of trkB and brain-derived neurotrophic factor are co-expressed in retinal pigmented epithelial cells and promote differentiated characteristics.". Brain Res.789 (2): 201–12. doi:10.1016/S0006-8993(97)01440-6. PMID9573364.
Yamada M, Ohnishi H, Sano S, Araki T, Nakatani A, Ikeuchi T, Hatanaka H (1999). "Brain-derived neurotrophic factor stimulates interactions of Shp2 with phosphatidylinositol 3-kinase and Grb2 in cultured cerebral cortical neurons.". J. Neurochem.73 (1): 41–9. doi:10.1046/j.1471-4159.1999.0730041.x. PMID10386953.
Ultsch MH, Wiesmann C, Simmons LC, Henrich J, Yang M, Reilly D, Bass SH, de Vos AM (1999). "Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC.". J. Mol. Biol.290 (1): 149–59. doi:10.1006/jmbi.1999.2816. PMID10388563.