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Gene Review

Ntrk1  -  neurotrophic tyrosine kinase, receptor,...

Rattus norvegicus

Synonyms: High affinity nerve growth factor receptor, Neurotrophic tyrosine kinase receptor type 1, Slow nerve growth factor receptor, Trk, Trk-A, ...
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Disease relevance of Ntrk1


Psychiatry related information on Ntrk1


High impact information on Ntrk1

  • The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors [11].
  • PMGS induces axon specification by enhancing TrkA activity locally, which triggers phosphatidylinositol-3-kinase (PI3K)- and Rac1-dependent inhibition of RhoA signaling and the consequent actin depolymerization in one neurite only [12].
  • Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination [13].
  • Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activity of the NGF receptor, TrkA, in both distal axons and cell bodies [14].
  • Here, we provide in vivo and in vitro evidence for the presence within DRG neurons of endosomes containing NGF, activated TrkA, and signaling proteins of the Rap1/Erk1/2, p38MAPK, and PI3K/Akt pathways [15].

Chemical compound and disease context of Ntrk1


Biological context of Ntrk1

  • In this assay, brain tissues were exposed to neutrophins and ligand-induced Trk tyrosine phosphorylation was measured [20].
  • Unlike the biological actions of other tyrosine kinase receptors, increased Trk receptor activity by adenosine resulted in increased cell survival [21].
  • Trk receptor transactivation is slower and results in a selective increase in activated Akt [21].
  • Mutagenesis identifies amino-terminal residues of nerve growth factor necessary for Trk receptor binding and biological activity [22].
  • Therefore, a complex homeostasis of p75-selective and Trk-selective signals may determine the fate of cells expressing both receptors [1].

Anatomical context of Ntrk1

  • PNT-1 stimulated survival and proliferation of MG87 fibroblasts expressing either TrkA, TrkB, or TrkC [23].
  • In contrast, responsiveness to the TrkA ligand NGF was absent in the ebmryo and increased during the first 2 weeks after birth in various brain areas, particularly in striatum, basal forebrain, and hippocampus [20].
  • In contrast, purified mutant H4D results in a nearly 1000-fold loss in TrkA binding at 4 degrees C relative to (1-118)hNGF, at least 10-fold less potency of TrkA autophosphorylation, and 30-fold loss of potency in PC12 cell differentiation [22].
  • Specific stimulation of TrkA receptors by receptor cross-linking, on the other hand, selectively stimulated neurite outgrowth and APP secretion but not APP mRNA levels, which were decreased [24].
  • Plasma membranes of the basal layer of stratified squamous cells contained TrkA [25].

Associations of Ntrk1 with chemical compounds


Physical interactions of Ntrk1

  • Down-regulation of the neurotrophin receptor TrkB following ligand binding. Evidence for an involvement of the proteasome and differential regulation of TrkA and TrkB [28].
  • These data are consistent with receptor allosterism, and prompted a search for TrkA/p75NTR complexes in the absence of NGF [29].
  • Coimmunoprecipitation assays showed that endogenous TrkA interacted with Mint2 in rat tissue homogenates, and immunohistochemical evidence revealed that Mint2 and TrkA colocalized in rat dorsal root ganglion neurons [30].

Enzymatic interactions of Ntrk1

  • Moreover, BMP-2 induced phosphorylated Trk immunoreactivity in cultured striatal neurones, suggesting that neurotrophins are involved in BMP-2 neurotrophic effects [31].
  • Moreover, on treatment with NGF, Trk-A is phosphorylated and early responsive genes such as NGFI-A, c-fos and c-jun are induced [32].

Regulatory relationships of Ntrk1

  • The p75NTR is a multifunctional type I membrane protein that promotes neurotrophin-induced neuronal survival and differentiation by forming a heteromeric co-receptor complex with the Trk receptors [33].
  • In addition, thymus cells expressed neuronal TrkA II mRNA and spleen cells expressed truncated TrkB mRNA [34].
  • Our studies show that the endosomal GTPase Rab7 controls the endosomal trafficking and neurite outgrowth signaling of TrkA [35].
  • NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis [36].
  • In addition to this, K-252a an inhibitor of Trk type kinase blocked the prevention of muscimol-induced LTD by brain-derived neurotrophic factor [37].

Other interactions of Ntrk1

  • We found that similar to sympathetic neurons, CEP-11004 increased the levels of the Trk receptor expressed in CGNs, TrkB [38].
  • Retinoic acid induces BDNF responsiveness of sympathetic neurons by alteration of Trk neurotrophin receptor expression [39].
  • Ovaries in both PCO and PCO anti-NGF groups decreased in size as well as in number and size of corpora lutea. mRNA expression of alpha1a-AR and TrkA in the ovaries was lower, whereas expression of alpha1b- and alpha1d-AR and TH was higher, in the PCO group than in controls [40].
  • Neurotrophin was found to phosphorylate Trk A and B, and the neurotrophin-induced enhancement of plasminogen-secretion was suppressed by protein kinase inhibitor, K252a [41].
  • Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival [38].

Analytical, diagnostic and therapeutic context of Ntrk1


  1. Differential cross-regulation of TrkA and TrkC tyrosine kinase receptors with p75. Ivanisevic, L., Banerjee, K., Saragovi, H.U. Oncogene (2003) [Pubmed]
  2. Cyclophosphamide induced cystitis alters neurotrophin and receptor tyrosine kinase expression in pelvic ganglia and bladder. Murray, E., Malley, S.E., Qiao, L.Y., Hu, V.Y., Vizzard, M.A. J. Urol. (2004) [Pubmed]
  3. Regulation of Trk receptors following contusion of the rat spinal cord. Liebl, D.J., Huang, W., Young, W., Parada, L.F. Exp. Neurol. (2001) [Pubmed]
  4. 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]
  5. Neurotrophins in cultured cells from periodontal tissues. Kurihara, H., Shinohara, H., Yoshino, H., Takeda, K., Shiba, H. J. Periodontol. (2003) [Pubmed]
  6. Progression of age-associated cognitive impairment correlates with quantitative and qualitative loss of TrkA receptor protein in nucleus basalis and cortex. Saragovi, H.U. J. Neurochem. (2005) [Pubmed]
  7. TrkA activation in the rat visual cortex by antirat trkA IgG prevents the effect of monocular deprivation. Pizzorusso, T., Berardi, N., Rossi, F.M., Viegi, A., Venstrom, K., Reichardt, L.F., Maffei, L. Eur. J. Neurosci. (1999) [Pubmed]
  8. Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits. Hasenöhrl, R.U., Söderstróm, S., Mohammed, A.H., Ebendal, T., Huston, J.P. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1997) [Pubmed]
  9. Expression of Trk isoforms in brain regions and in the striatum of patients with Alzheimer's disease. Dubus, P., Faucheux, B., Boissière, F., Groppi, A., Vital, C., Vital, A., Agid, Y., Hirsch, E.C., Merlio, J.P. Exp. Neurol. (2000) [Pubmed]
  10. Lithium increases nerve growth factor levels in the rat hippocampus in an animal model of mania. Frey, B.N., Andreazza, A.C., Rosa, A.R., Martins, M.R., Valvassori, S.S., Réus, G.Z., Hatch, J.P., Quevedo, J., Kapczinski, F. Behavioural pharmacology. (2006) [Pubmed]
  11. Neurotrophin-evoked rapid excitation through TrkB receptors. Kafitz, K.W., Rose, C.R., Thoenen, H., Konnerth, A. Nature (1999) [Pubmed]
  12. Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Da Silva, J.S., Hasegawa, T., Miyagi, T., Dotti, C.G., Abad-Rodriguez, J. Nat. Neurosci. (2005) [Pubmed]
  13. Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination. Arévalo, J.C., Waite, J., Rajagopal, R., Beyna, M., Chen, Z.Y., Lee, F.S., Chao, M.V. Neuron (2006) [Pubmed]
  14. Evidence in support of signaling endosome-based retrograde survival of sympathetic neurons. Ye, H., Kuruvilla, R., Zweifel, L.S., Ginty, D.D. Neuron (2003) [Pubmed]
  15. NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals. Delcroix, J.D., Valletta, J.S., Wu, C., Hunt, S.J., Kowal, A.S., Mobley, W.C. Neuron (2003) [Pubmed]
  16. Neurotrophins protect against cytosine arabinoside-induced apoptosis of immature rat cerebellar neurons. Leeds, P., Leng, Y., Chalecka-Franaszek, E., Chuang, D.M. Neurochem. Int. (2005) [Pubmed]
  17. Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo. Li, X.D., Arias, E., Jonnala, R.R., Mruthinti, S., Buccafusco, J.J. J. Mol. Neurosci. (2005) [Pubmed]
  18. TrkA induces differentiation but not apoptosis in C6-2B glioma cells. Pflug, B.R., Colangelo, A.M., Tornatore, C., Mocchetti, I. J. Neurosci. Res. (2001) [Pubmed]
  19. P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation. Arthur, D.B., Akassoglou, K., Insel, P.A. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  20. Regulated neurotrophin receptor responsiveness during neuronal migrationand early differentiation. Knüsel, B., Rabin, S.J., Hefti, F., Kaplan, D.R. J. Neurosci. (1994) [Pubmed]
  21. Distinctive features of Trk neurotrophin receptor transactivation by G protein-coupled receptors. Lee, F.S., Rajagopal, R., Chao, M.V. Cytokine Growth Factor Rev. (2002) [Pubmed]
  22. Mutagenesis identifies amino-terminal residues of nerve growth factor necessary for Trk receptor binding and biological activity. Shih, A., Laramee, G.R., Schmelzer, C.H., Burton, L.E., Winslow, J.W. J. Biol. Chem. (1994) [Pubmed]
  23. 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]
  24. p75 and TrkA receptor signaling independently regulate amyloid precursor protein mRNA expression, isoform composition, and protein secretion in PC12 cells. Rossner, S., Ueberham, U., Schliebs, R., Perez-Polo, J.R., Bigl, V. J. Neurochem. (1998) [Pubmed]
  25. Role of neurotrophins and neurotrophin receptors in rat conjunctival goblet cell secretion and proliferation. Ríos, J.D., Ghinelli, E., Gu, J., Hodges, R.R., Dartt, D.A. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  26. Gangliosides activate Trk receptors by inducing the release of neurotrophins. Rabin, S.J., Bachis, A., Mocchetti, I. J. Biol. Chem. (2002) [Pubmed]
  27. Brain-derived neurotrophic factor binding to the p75 neurotrophin receptor reduces TrkA signaling while increasing serine phosphorylation in the TrkA intracellular domain. MacPhee, I.J., Barker, P.A. J. Biol. Chem. (1997) [Pubmed]
  28. 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]
  29. Reciprocal modulation of TrkA and p75NTR affinity states is mediated by direct receptor interactions. Ross, G.M., Shamovsky, I.L., Lawrance, G., Solc, M., Dostaler, S.M., Weaver, D.F., Riopelle, R.J. Eur. J. Neurosci. (1998) [Pubmed]
  30. Interaction of Mint2 with TrkA is involved in regulation of nerve growth factor-induced neurite outgrowth. Zhang, Y., Wang, Y.G., Zhang, Q., Liu, X.J., Liu, X., Jiao, L., Zhu, W., Zhang, Z.H., Zhao, X.L., He, C. J. Biol. Chem. (2009) [Pubmed]
  31. Brain-derived neurotrophic factor (BDNF) mediates bone morphogenetic protein-2 (BMP-2) effects on cultured striatal neurones. Gratacòs, E., Checa, N., Pérez-Navarro, E., Alberch, J. J. Neurochem. (2001) [Pubmed]
  32. Pancreatic acinar AR42J cells express functional nerve growth factor receptors. Miralles, F., Czernichow, P., Scharfmann, R. J. Endocrinol. (1999) [Pubmed]
  33. Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor. Jung, K.M., Tan, S., Landman, N., Petrova, K., Murray, S., Lewis, R., Kim, P.K., Kim, D.S., Ryu, S.H., Chao, M.V., Kim, T.W. J. Biol. Chem. (2003) [Pubmed]
  34. 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]
  35. The small GTPase Rab7 controls the endosomal trafficking and neuritogenic signaling of the nerve growth factor receptor TrkA. Saxena, S., Bucci, C., Weis, J., Kruttgen, A. J. Neurosci. (2005) [Pubmed]
  36. NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis. Belliveau, D.J., Krivko, I., Kohn, J., Lachance, C., Pozniak, C., Rusakov, D., Kaplan, D., Miller, F.D. J. Cell Biol. (1997) [Pubmed]
  37. Prevention of muscimol-induced long-term depression by brain-derived neurotrophic factor. Akhondzadeh, S., Stone, T. Prog. Neuropsychopharmacol. Biol. Psychiatry (1999) [Pubmed]
  38. 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]
  39. Retinoic acid induces BDNF responsiveness of sympathetic neurons by alteration of Trk neurotrophin receptor expression. Kobayashi, M., Kurihara, K., Matsuoka, I. FEBS Lett. (1994) [Pubmed]
  40. Effect of anti-NGF on ovarian expression of alpha1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries. Manni, L., Holmäng, A., Cajander, S., Lundeberg, T., Aloe, L., Stener-Victorin, E. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  41. Neurotrophins regulate the function of cultured microglia. Nakajima, K., Kikuchi, Y., Ikoma, E., Honda, S., Ishikawa, M., Liu, Y., Kohsaka, S. Glia (1998) [Pubmed]
  42. Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling. Geetha, T., Wooten, M.W. J. Biol. Chem. (2003) [Pubmed]
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