TrkB受容体、TrkBレセプター

関: BDNF receptor

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/01 22:49:29」(JST)

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Tropomyosin receptor kinase B (TrkB),^[1] also known as Tryosine receptor kinase B,^[1] or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene.^[1]^[2] TrkB is a receptor for brain-derived neurotrophic factor (BDNF).

Function

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).^[1] 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. ^[3]

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.

TrkB signaling

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.

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.

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.

Interactions

TrkB has been shown to interact with:

Brain-derived neurotrophic factor (BDNF),^[4]^[5]
FYN,^[6]
NCK2,^[7]
PLCG1,^[7]^[8]
Sequestosome 1,^[9] and
SHC3.^[7]^[10]

Ligands

Agonists

Brain-derived neurotrophic factor (BDNF)
Neurotrophin-3 (NT-3)
Neurotrophin-4 (NT-4)
N-Acetylserotonin
HIOC
Amitriptyline^[11]
7,8-Dihydroxyflavone
7,8,3'-Trihydroxyflavone
4'-Dimethylamino-7,8-dihydroxyflavone^[12]
Deoxygedunin^[13]
LM-22A4
TDP6
3,7-Dihydroxyflavone
3,7,8,2'-Tetrahydroxyflavone
4'-Dimethylamino-7,8-dihydroxyflavone
5,7,8-Trihydroxyflavone
7,3′-Dihydroxyflavone
7,8,2'-Trihydroxyflavone

Antagonists

3,5,7,8,3',4'-Hexahydroxylatedflavone
ANA-12
Cyclotraxin B

References

^ ^a ^b ^c ^d Malenka 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. –. ISBN 9780071481274. 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 X, Ikegaki N, White P, Yamashiro D, Nycum L et al. (January 1995). "Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2)". Genomics 25 (2): 538–46. doi:10.1016/0888-7543(95)80055-Q. PMID 7789988.
^ "BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion.".
^ Haniu M, Montestruque S, Bures E, Talvenheimo J, Toso R, Lewis-Sandy S et al. (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. PMID 9312147.
^ Naylor R, Robertson A, Allen S, Sessions R, Clarke A, Mason G et al. (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. PMID 11855816.
^ Iwasaki Y, Gay B, Wada K, Koizumi S (July 1998). "Association of the Src family tyrosine kinase Fyn with TrkB". J. Neurochem. 71 (1): 106–11. doi:10.1046/j.1471-4159.1998.71010106.x. PMID 9648856.
^ ^a ^b ^c Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H et al. (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. PMID 12074588.
^ Meakin S, MacDonald J, Gryz E, Kubu C, Verdi J (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. PMID 10092678.
^ Geetha T, Wooten M (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. PMID 12471037.
^ 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. PMID 9507002.
^ Jang S, Liu X, Chan C, Weinshenker D, Hall R, Xiao G et al. (2009). "Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity". Chem. Biol. 16 (6): 644–56. doi:10.1016/j.chembiol.2009.05.010. PMC 2844702. PMID 19549602.
^ Liu X, Chan C, Jang S, Pradoldej S, Huang J, He K et al. (November 2010). "A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect". J. Med. Chem. 53 (23): 8274–86. doi:10.1021/jm101206p. PMID 21073191.
^ Jang S, Liu X, Chan C, France S, Sayeed I, Tang W et al. (2010). "Deoxygedunin, a natural product with potent neurotrophic activity in mice". PLoS ONE 5 (7): e11528. doi:10.1371/journal.pone.0011528. PMC 2903477. PMID 20644624.

External links

Memories are made of this molecule - New Scientist, 15 January 2007.

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Japanese Journal

中枢によるインスリン感受性制御 : BDNFを中心に (特集ホルモン作用と臓器相関)

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NAID 40019957579

Calorie Restriction Improves Cognitive Decline via Up-Regulation of Brain-Derived Neurotrophic Factor:Tropomyosin-Related Kinase B in Hippocampus of Obesity-Induced Hypertensive Rats

Kishi Takuya,Hirooka Yoshitaka,Nagayama Tomomi,Isegawa Kengo,Katsuki Masato,Takesue Ko,Sunagawa Kenji
International Heart Journal, 2014
… The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. … We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). …
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Brain-derived neurotrophic factor promotes angiogenesis via oxidative stress in human vascular endothelial cells: Implication for atherogenesis?

Yamawaki Hideyuki
Microvascular Reviews and Communications 7(1), 32a-32a, 2014
… BDNF-increased ROS generation and NOX activity were inhibited by K252a, an inhibitor of tropomyosin-related kinase B (TrkB) receptor. …
NAID 130004678488

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★リンクテーブル★

リンク元	「BDNF receptor」「trkB受容体」「TrkBレセプター」

「BDNF receptor」

Neurotrophic tyrosine kinase, receptor, type 2
	; PDB rendering based on 1hcf.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1HCF, 1WWB, 2MFQ, 4ASZ, 4AT3, 4AT4, 4AT5
Identifiers
Symbols	NTRK2 ; GP145-TrkB; TRKB; trk-B
External IDs	OMIM: 600456 MGI: 97384 HomoloGene: 4504 ChEMBL: 4898 GeneCards: NTRK2 Gene
EC number	2.7.10.1
Gene ontology
Molecular function	• ATP binding; • protein homodimerization activity; • neurotrophin binding; • ephrin receptor binding; • brain-derived neurotrophic factor binding; • brain-derived neurotrophic factor-activated receptor activity;
Cellular component	• cytosol; • integral component of plasma membrane; • cell surface; • endosome membrane; • postsynaptic density; • growth cone; • neuronal cell body; • terminal bouton; • dendritic spine; • receptor complex; • postsynaptic membrane; • presynaptic active zone; • excitatory synapse;
Biological process	• vasculogenesis; • neuron migration; • transmembrane receptor protein tyrosine kinase signaling pathway; • activation of adenylate cyclase activity; • neuromuscular junction development; • aging; • learning; • long-term memory; • feeding behavior; • positive regulation of cell proliferation; • positive regulation of gene expression; • positive regulation of neuron projection development; • response to auditory stimulus; • glutamate secretion; • positive regulation of phosphatidylinositol 3-kinase signaling; • peptidyl-tyrosine phosphorylation; • central nervous system neuron development; • cerebral cortex development; • neuron differentiation; • brain-derived neurotrophic factor receptor signaling pathway; • regulation of Rac GTPase activity; • calcium-mediated signaling using intracellular calcium source; • mechanoreceptor differentiation; • positive regulation of MAPK cascade; • negative regulation of neuron apoptotic process; • retinal rod cell development; • protein autophosphorylation; • regulation of neurotransmitter secretion; • neurotrophin TRK receptor signaling pathway; • oligodendrocyte differentiation; • peripheral nervous system neuron development; • positive regulation of axonogenesis; • regulation of dendrite development; • regulation of protein kinase B signaling; • positive regulation of synaptic transmission, glutamatergic; • long-term synaptic potentiation; • negative regulation of anoikis;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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