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Gene Review

Ntrk2  -  neurotrophic tyrosine kinase, receptor,...

Rattus norvegicus

Synonyms: BDNF/NT-3 growth factors receptor, Neurotrophic tyrosine kinase receptor type 2, RATTRKB1, TRKB1, Tkrb, ...
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Disease relevance of Ntrk2


Psychiatry related information on Ntrk2

  • We examined the time course of BDNF and TrkB expression after 1, 3, 5, 7 or 14 days in one of three conditions: (1) an "acrobatic" motor skill learning condition (AC), (2) a motor activity condition (moderately paced running on a flat track; MC) and (3) an inactive social-only control (SC) that served as a baseline group [6].

High impact information on Ntrk2

  • Whereas TrkB.t1-infected rats showed normal within-session extinction, their retention of extinction was impaired, suggesting that amygdala TrkB activation is required for the consolidation of stable extinction memories [4].
  • In addition, cAMP facilitated trafficking of TrkB to dendritic spines, possibly by promoting its interaction with synaptic scaffolding protein PSD-95 [7].
  • Actions of the truncated TrkB receptor did not involve unmasking of endogenous TrkC signaling [8].
  • These results indicate a causal link of synapsin phosphorylation via BDNF, TrkB receptors and MAP kinase with downstream facilitation of neurotransmitter release [9].
  • We transfected ferret visual cortical slices with full-length and truncated TrkB receptors to examine their roles in regulating cortical dendrite development [8].

Chemical compound and disease context of Ntrk2


Biological context of Ntrk2


Anatomical context of Ntrk2


Associations of Ntrk2 with chemical compounds

  • However, the increased amplitude was postsynaptic in origin because it was selectively blocked by intracellular injection of the tyrosine kinase receptor (Ntrk2/TrkB) inhibitor K-252a and potentiated by injection of the phosphatase inhibitor okadaic acid [18].
  • BDNF treatment of high TrkB-expressing TB8 (Tet-) and TB3 (Tet-) cells blocked drug-induced cell death in a dose-dependent manner [1].
  • Astrocytes in culture express the full-length Trk-B receptor and respond to brain derived neurotrophic factor by changing intracellular calcium levels: effect of ethanol exposure in rats [19].
  • In Shc signaling, NGF, but not BDNF, displayed interactions between Trk and Shc in a phenylarsine oxide (PAO; an inhibitor of tyrosine phosphatase)-dependent manner in TrkB-expressing PC12 cells [20].
  • We suggest that NMDA activates the TrkB receptor via a BDNF autocrine loop, resulting in neuronal survival [5].

Physical interactions of Ntrk2

  • BDNF binds to TrkB, a receptor tyrosine kinase, which results in the activation of a variety of signaling molecules to exert the various functions of BDNF [21].
  • The transcellular induction of NPY suggests a source-to-sink model for axonal transport and a local cortical redistribution of TrkB ligands to interneurons competent for NPY expression [22].
  • Down-regulation of the neurotrophin receptor TrkB following ligand binding. Evidence for an involvement of the proteasome and differential regulation of TrkA and TrkB [23].
  • Fyn was coimmunoprecipitated with TrkB and NR2B, and this association was increased in well-trained rats compared with control animals [24].
  • A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy [25].

Enzymatic interactions of Ntrk2

  • We conclude that phospholipase C-gamma 1 is directly phosphorylated by TrkB [26].
  • The results showed that the fluorescent intensity of TrkB and phosphorylated TrkB in the cytoplasm and the fluorescent intensity of MARK in both cytoplasma and nucleus of the neurons were significantly increased in the presence of BDNF [3].

Regulatory relationships of Ntrk2

  • In addition, thymus cells expressed neuronal TrkA II mRNA and spleen cells expressed truncated TrkB mRNA [27].
  • Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth [28].
  • NT-3 induced the tyrosine phosphorylation of TrkB in naive cells, but not in differentiated cells [29].
  • Ectopic expression of a chimeric colony-stimulating factor-1/TrkB-receptor promotes CSF-1-dependent survival of cultured sympathetic neurons [30].

Other interactions of Ntrk2

  • Together, these data suggest that an antagonistic interplay of p75NTR and TrkB receptor signaling, possibly modulated by selective BDNF processing, mediates SGN death in vivo [13].
  • We provide in vivo evidence demonstrating that degenerating SGNs induced an augmented p75NTR expression and a coincident reduction of TrkB expression in their peripheral processes [13].
  • We found that similar to sympathetic neurons, CEP-11004 increased the levels of the Trk receptor expressed in CGNs, TrkB [31].
  • In addition, NT-3 was able to phosphorylate the BDNF receptor, TrkB but only at higher concentration (50 ng/ml) [32].
  • Following activation of TrkB, phospholipase C-gamma 1 is phosphorylated on Tyr-783, Tyr-771, and Tyr-1254 [26].

Analytical, diagnostic and therapeutic context of Ntrk2


  1. Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3'-kinase pathway. Jaboin, J., Kim, C.J., Kaplan, D.R., Thiele, C.J. Cancer Res. (2002) [Pubmed]
  2. Changes in retinal expression of neurotrophins and neurotrophin receptors induced by ocular hypertension. Rudzinski, M., Wong, T.P., Saragovi, H.U. J. Neurobiol. (2004) [Pubmed]
  3. Cellular levels of TrkB and MAPK in the neuroprotective role of BDNF for embryonic rat cortical neurons against hypoxia in vitro. Meng, M., Zhiling, W., Hui, Z., Shengfu, L., Dan, Y., Jiping, H. Int. J. Dev. Neurosci. (2005) [Pubmed]
  4. Amygdala BDNF signaling is required for consolidation but not encoding of extinction. Chhatwal, J.P., Stanek-Rattiner, L., Davis, M., Ressler, K.J. Nat. Neurosci. (2006) [Pubmed]
  5. Activity-dependent release of brain-derived neurotrophic factor underlies the neuroprotective effect of N-methyl-D-aspartate. Marini, A.M., Rabin, S.J., Lipsky, R.H., Mocchetti, I. J. Biol. Chem. (1998) [Pubmed]
  6. Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise. Klintsova, A.Y., Dickson, E., Yoshida, R., Greenough, W.T. Brain Res. (2004) [Pubmed]
  7. Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons. Ji, Y., Pang, P.T., Feng, L., Lu, B. Nat. Neurosci. (2005) [Pubmed]
  8. Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth. Yacoubian, T.A., Lo, D.C. Nat. Neurosci. (2000) [Pubmed]
  9. Synapsins as mediators of BDNF-enhanced neurotransmitter release. Jovanovic, J.N., Czernik, A.J., Fienberg, A.A., Greengard, P., Sihra, T.S. Nat. Neurosci. (2000) [Pubmed]
  10. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. D'Cruz, B.J., Fertig, K.C., Filiano, A.J., Hicks, S.D., DeFranco, D.B., Callaway, C.W. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  11. Involvement of the brain-derived neurotrophic factor/TrkB pathway in neuroprotecive effect of cyclosporin A in forebrain ischemia. Miyata, K., Omori, N., Uchino, H., Yamaguchi, T., Isshiki, A., Shibasaki, F. Neuroscience (2001) [Pubmed]
  12. Expression of p75NGFR TrkA, and TrkB mRNA in rat C6 glioma and type I astrocyte cultures. Hutton, L.A., deVellis, J., Perez-Polo, J.R. J. Neurosci. Res. (1992) [Pubmed]
  13. Aminoglycoside-induced degeneration of adult spiral ganglion neurons involves differential modulation of tyrosine kinase B and p75 neurotrophin receptor signaling. Tan, J., Shepherd, R.K. Am. J. Pathol. (2006) [Pubmed]
  14. Long-term potentiation in the dentate gyrus of the rat hippocampus is accompanied by brain-derived neurotrophic factor-induced activation of TrkB. Gooney, M., Lynch, M.A. J. Neurochem. (2001) [Pubmed]
  15. BDNF down-regulates neurotrophin responsiveness, TrkB protein and TrkB mRNA levels in cultured rat hippocampal neurons. Frank, L., Ventimiglia, R., Anderson, K., Lindsay, R.M., Rudge, J.S. Eur. J. Neurosci. (1996) [Pubmed]
  16. Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo. Ilag, L.L., Curtis, R., Glass, D., Funakoshi, H., Tobkes, N.J., Ryan, T.E., Acheson, A., Lindsay, R.M., Persson, H., Yancopoulos, G.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  17. Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor. Hartmann, M., Brigadski, T., Erdmann, K.S., Holtmann, B., Sendtner, M., Narz, F., Lessmann, V. J. Cell. Sci. (2004) [Pubmed]
  18. Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Levine, E.S., Dreyfus, C.F., Black, I.B., Plummer, M.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  19. Astrocytes in culture express the full-length Trk-B receptor and respond to brain derived neurotrophic factor by changing intracellular calcium levels: effect of ethanol exposure in rats. Climent, E., Sancho-Tello, M., Miñana, R., Barettino, D., Guerri, C. Neurosci. Lett. (2000) [Pubmed]
  20. Distinct usages of phospholipase C gamma and Shc in intracellular signaling stimulated by neurotrophins. Yamada, M., Numakawa, T., Koshimizu, H., Tanabe, K., Wada, K., Koizumi, S., Hatanaka, H. Brain Res. (2002) [Pubmed]
  21. Shp-2 specifically regulates several tyrosine-phosphorylated proteins in brain-derived neurotrophic factor signaling in cultured cerebral cortical neurons. Araki, T., Yamada, M., Ohnishi, H., Sano, S., Uetsuki, T., Hatanaka, H. J. Neurochem. (2000) [Pubmed]
  22. Transcellular induction of neuropeptide Y expression by NT4 and BDNF. Wirth, M.J., Patz, S., Wahle, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  23. Down-regulation of the neurotrophin receptor TrkB following ligand binding. Evidence for an involvement of the proteasome and differential regulation of TrkA and TrkB. Sommerfeld, M.T., Schweigreiter, R., Barde, Y.A., Hoppe, E. J. Biol. Chem. (2000) [Pubmed]
  24. Involvement of BDNF receptor TrkB in spatial memory formation. Mizuno, M., Yamada, K., He, J., Nakajima, A., Nabeshima, T. Learn. Mem. (2003) [Pubmed]
  25. A possible role for BDNF, NT-4 and TrkB in the spinal cord and muscle of rat subjected to mechanical overload, bupivacaine injection and axotomy. Sakuma, K., Watanabe, K., Sano, M., Uramoto, I., Nakano, H., Li, Y.J., Kaneda, S., Sorimachi, Y., Yoshimoto, K., Yasuhara, M., Totsuka, T. Brain Res. (2001) [Pubmed]
  26. Identification of TrkB autophosphorylation sites and evidence that phospholipase C-gamma 1 is a substrate of the TrkB receptor. Middlemas, D.S., Meisenhelder, J., Hunter, T. J. Biol. Chem. (1994) [Pubmed]
  27. Expression of mRNA encoding neurotrophins and neurotrophin receptors in rat thymus, spleen tissue and immunocompetent cells. Regulation of neurotrophin-4 mRNA expression by mitogens and leukotriene B4. Laurenzi, M.A., Barbany, G., Timmusk, T., Lindgren, J.A., Persson, H. Eur. J. Biochem. (1994) [Pubmed]
  28. Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions. Wahle, P., Di Cristo, G., Schwerdtfeger, G., Engelhardt, M., Berardi, N., Maffei, L. Development (2003) [Pubmed]
  29. Comparison of survival-promoting effects of brain-derived neurotrophic factor and neurotrophin-3 on PC12h cells stably expressing TrkB receptor. Nakatani, A., Yamada, M., Asada, A., Okada, M., Ikeuchi, T., Hatanaka, H. J. Biochem. (1998) [Pubmed]
  30. Ectopic expression of a chimeric colony-stimulating factor-1/TrkB-receptor promotes CSF-1-dependent survival of cultured sympathetic neurons. Erdmann, K.S., Kaiser, A.D., Klinz, F.J., Zhong, J., Krautwald, S., Heumann, R. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  31. Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival. Wang, L.H., Paden, A.J., Johnson, E.M. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  32. Constitutive phosphorylation of TrkC receptors in cultured cerebellar granule neurons might be responsible for the inability of NT-3 to increase neuronal survival and to activate p21 Ras. Zirrgiebel, U., Lindholm, D. Neurochem. Res. (1996) [Pubmed]
  33. Synaptic and extrasynaptic localization of brain-derived neurotrophic factor and the tyrosine kinase B receptor in cultured hippocampal neurons. Swanwick, C.C., Harrison, M.B., Kapur, J. J. Comp. Neurol. (2004) [Pubmed]
  34. Up-regulation of tyrosine kinase (Trka, Trkb) receptor expression and phosphorylation in lumbosacral dorsal root ganglia after chronic spinal cord (T8-T10) injury. Qiao, L., Vizzard, M.A. J. Comp. Neurol. (2002) [Pubmed]
  35. The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes. Xu, B., Michalski, B., Racine, R.J., Fahnestock, M. Neuroscience (2004) [Pubmed]
  36. Enriched environment during adolescence changes brain-derived neurotrophic factor and TrkB levels in the rat visual system but does not offer neuroprotection to retinal ganglion cells following axotomy. Franklin, T.B., Murphy, J.A., Myers, T.L., Clarke, D.B., Currie, R.W. Brain Res. (2006) [Pubmed]
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