The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NTRK3  -  neurotrophic tyrosine kinase, receptor,...

Homo sapiens

Synonyms: GP145-TrkC, NT-3 growth factor receptor, Neurotrophic tyrosine kinase receptor type 3, TRKC, Trk-C, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NTRK3


Psychiatry related information on NTRK3


High impact information on NTRK3

  • Our studies indicate that a chimaeric PTK is expressed in CFS and this may contribute to oncogenesis by dysregulation of NTRK3 signal transduction pathways [1].
  • Biochemical analysis indicates that phosphorylation at the Shc site positively regulates autophosphorylation of TrkB, but not of TrkC [7].
  • Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate [8].
  • RESULTS: Neither neurotrophins nor their receptors were identified in immature postmigrational ENS progenitors at 7 weeks' fetal developmental age; however, TrkC and TrkA were specifically localized to developing ENS cells after 19 developmental weeks [9].
  • A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin [10].

Chemical compound and disease context of NTRK3

  • We tested four histologically confirmed cases of SBC for the presence of the ETV6-NTRK3 gene fusion and then applied the FISH assay to tissue microarrays (TMAs) in order to screen 481 cases of formalin-fixed, paraffin-embedded invasive breast carcinomas of various histologic subtypes [11].
  • Human melanoma TrkC: its association with a purine-analog-sensitive kinase activity [12].
  • Here we demonstrate that, by using sensitive immune-complex kinase assays in human brain-metastatic (70W) melanoma cells, TrkC receptors associate with a kinase activity exhibiting a dose-dependent susceptibility to inhibition by the purine-analogs 6-thioguanine and 2-aminopurine [12].

Biological context of NTRK3


Anatomical context of NTRK3

  • Mutation analysis of NTRK2 and NTRK3, encoding 2 tyrosine kinase receptors, in sporadic human medullary thyroid carcinoma reveals novel sequence variants [2].
  • Immunoreactivity for both catalytic and truncated TrkC receptor was observed in promyelocytes, myelocytes, some polymorphonuclear cells and megacaryocytes [16].
  • Using reverse transcription-polymerase chain reaction, all transcripts encoding for catalytic and truncated human TrkB or TrkC receptors were detected together with trkAI transcripts, whereas trkAII transcripts were found only in control nerve tissues [16].
  • Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils [17].
  • A 3.5% macrophages displayed immunoreactivity for TrkA-receptor protein, 10% for TrkB-receptor protein (full length isoform), and 2% for TrkC-receptor protein [18].

Associations of NTRK3 with chemical compounds

  • Moreover, ETV6-NTRK3 has PTK activity and is autophosphorylated on tyrosine residues [14].
  • We studied immunohistochemical expression of NTRK3, and conducted a reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the ETV6-NTRK3 fusion transcripts using archival formalin-fixed paraffin-embedded tissues from 10 CIFSs [19].
  • Compared with previous findings in IDCs, SCAs are characterized by a relatively low number of GAs, a low proliferative rate, infrequent HER2/neu protein overexpression, decreased steroid hormone receptor expression, and expression of ETV6-NTRK3 fusion gene [3].
  • Neurotrophin-3/TrkC-induced apoptosis is inhibited by the mitogen-activated protein (MAP) kinase (MAPK) pharmacologic antagonists SB203580 and PD98059 [20].
  • RA treatment of SH-SY5Y cells induces the appearance of functional Trk B and Trk C receptors [21].

Enzymatic interactions of NTRK3


Regulatory relationships of NTRK3


Other interactions of NTRK3

  • Analysis of mRNA revealed the expression of ETV6-NTRK3 chimaeric transcripts in all three CFS tumours analysed [1].
  • In later stages of MTC, NTRK2 expression was reduced while NTRK3 expression was increased [2].
  • Mutants of the three NTRK3 PTK activation-loop tyrosines had variable PTK activity but had limited to absent transformation activity [14].
  • Aganglionic HD intestine lacked intense and specific TrkC and BDNF enteric ganglionic immunoreactivity [23].
  • RNA extraction was performed on formalin-fixed, paraffin-embedded tissue from 7 mixed epithelial and stromal tumors followed by reverse-transcription polymerase chain reaction to detect the ETV6-NTRK3 gene fusion [24].

Analytical, diagnostic and therapeutic context of NTRK3


  1. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Knezevich, S.R., McFadden, D.E., Tao, W., Lim, J.F., Sorensen, P.H. Nat. Genet. (1998) [Pubmed]
  2. Mutation analysis of NTRK2 and NTRK3, encoding 2 tyrosine kinase receptors, in sporadic human medullary thyroid carcinoma reveals novel sequence variants. Gimm, O., Dziema, H., Brown, J., de la Puente, A., Hoang-Vu, C., Dralle, H., Plass, C., Eng, C. Int. J. Cancer (2001) [Pubmed]
  3. Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry. Diallo, R., Schaefer, K.L., Bankfalvi, A., Decker, T., Ruhnke, M., Wülfing, P., Jackisch, C., Luttges, J., Sorensen, P.H., Singh, M., Poremba, C. Hum. Pathol. (2003) [Pubmed]
  4. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Eguchi, M., Eguchi-Ishimae, M., Tojo, A., Morishita, K., Suzuki, K., Sato, Y., Kudoh, S., Tanaka, K., Setoyama, M., Nagamura, F., Asano, S., Kamada, N. Blood (1999) [Pubmed]
  5. Expression of TrkA, TrkB and TrkC in human neuroblastomas. Brodeur, G.M., Nakagawara, A., Yamashiro, D.J., Ikegaki, N., Liu, X.G., Azar, C.G., Lee, C.P., Evans, A.E. J. Neurooncol. (1997) [Pubmed]
  6. 5' UTR-region SNP in the NTRK3 gene is associated with panic disorder. Armengol, L., Gratacòs, M., Pujana, M.A., Ribasés, M., Martín-Santos, R., Estivill, X. Mol. Psychiatry (2002) [Pubmed]
  7. Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons. Postigo, A., Calella, A.M., Fritzsch, B., Knipper, M., Katz, D., Eilers, A., Schimmang, T., Lewin, G.R., Klein, R., Minichiello, L. Genes Dev. (2002) [Pubmed]
  8. Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate. Moqrich, A., Earley, T.J., Watson, J., Andahazy, M., Backus, C., Martin-Zanca, D., Wright, D.E., Reichardt, L.F., Patapoutian, A. Nat. Neurosci. (2004) [Pubmed]
  9. Localization of neurotrophins and their high-affinity receptors during human enteric nervous system development. Hoehner, J.C., Wester, T., Påhlman, S., Olsen, L. Gastroenterology (1996) [Pubmed]
  10. A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin. Esteban, P.F., Yoon, H.Y., Becker, J., Dorsey, S.G., Caprari, P., Palko, M.E., Coppola, V., Saragovi, H.U., Randazzo, P.A., Tessarollo, L. J. Cell Biol. (2006) [Pubmed]
  11. A fluorescence in situ hybridization study of ETV6-NTRK3 fusion gene in secretory breast carcinoma. Makretsov, N., He, M., Hayes, M., Chia, S., Horsman, D.E., Sorensen, P.H., Huntsman, D.G. Genes Chromosomes Cancer (2004) [Pubmed]
  12. Human melanoma TrkC: its association with a purine-analog-sensitive kinase activity. Marchetti, D., Murry, B., Galjour, J., Wilke-Greiter, A. J. Cell. Biochem. (2003) [Pubmed]
  13. Additional complexity on human chromosome 15q: identification of a set of newly recognized duplicons (LCR15) on 15q11-q13, 15q24, and 15q26. Pujana, M.A., Nadal, M., Gratacòs, M., Peral, B., Csiszar, K., González-Sarmiento, R., Sumoy, L., Estivill, X. Genome Res. (2001) [Pubmed]
  14. The ETV6-NTRK3 gene fusion encodes a chimeric protein tyrosine kinase that transforms NIH3T3 cells. Wai, D.H., Knezevich, S.R., Lucas, T., Jansen, B., Kay, R.J., Sorensen, P.H. Oncogene (2000) [Pubmed]
  15. ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages. Lannon, C.L., Sorensen, P.H. Semin. Cancer Biol. (2005) [Pubmed]
  16. Expression of neurotrophins and their receptors in human bone marrow. Labouyrie, E., Dubus, P., Groppi, A., Mahon, F.X., Ferrer, J., Parrens, M., Reiffers, J., de Mascarel, A., Merlio, J.P. Am. J. Pathol. (1999) [Pubmed]
  17. Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils. Noga, O., Englmann, C., Hanf, G., Grützkau, A., Guhl, S., Kunkel, G. Clin. Exp. Allergy (2002) [Pubmed]
  18. Neurotrophin and neurotrophin receptor expression in alveolar macrophages: an immunocytochemical study. Ricci, A., Greco, S., Mariotta, S., Felici, L., Amenta, F., Bronzetti, E. Growth Factors (2000) [Pubmed]
  19. Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues. Sheng, W.Q., Hisaoka, M., Okamoto, S., Tanaka, A., Meis-Kindblom, J.M., Kindblom, L.G., Ishida, T., Nojima, T., Hashimoto, H. Am. J. Clin. Pathol. (2001) [Pubmed]
  20. A novel role for extracellular signal-regulated kinase 5 and myocyte enhancer factor 2 in medulloblastoma cell death. Sturla, L.M., Cowan, C.W., Guenther, L., Castellino, R.C., Kim, J.Y., Pomeroy, S.L. Cancer Res. (2005) [Pubmed]
  21. Extracellular-regulated kinases and phosphatidylinositol 3-kinase are involved in brain-derived neurotrophic factor-mediated survival and neuritogenesis of the neuroblastoma cell line SH-SY5Y. Encinas, M., Iglesias, M., Llecha, N., Comella, J.X. J. Neurochem. (1999) [Pubmed]
  22. The neurotrophin-3 receptor TrkC directly phosphorylates and activates the nucleotide exchange factor Dbs to enhance Schwann cell migration. Yamauchi, J., Chan, J.R., Miyamoto, Y., Tsujimoto, G., Shooter, E.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  23. Alterations in neurotrophin and neurotrophin-receptor localization in Hirschsprung's disease. Hoehner, J.C., Wester, T., Påhlman, S., Olsen, L. J. Pediatr. Surg. (1996) [Pubmed]
  24. Mixed epithelial and stromal tumor of the kidney lacks the genetic alterations of cellular congenital mesoblastic nephroma. Pierson, C.R., Schober, M.S., Wallis, T., Sarkar, F.H., Sorensen, P.H., Eble, J.N., Srigley, J.R., Jones, E.C., Grignon, D.J., Adsay, V. Hum. Pathol. (2001) [Pubmed]
  25. Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Bourgeois, J.M., Knezevich, S.R., Mathers, J.A., Sorensen, P.H. Am. J. Surg. Pathol. (2000) [Pubmed]
  26. Non-resectable congenital tumors with the ETV6-NTRK3 gene fusion are highly responsive to chemotherapy. McCahon, E., Sorensen, P.H., Davis, J.H., Rogers, P.C., Schultz, K.R. Med. Pediatr. Oncol. (2003) [Pubmed]
  27. Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature. Arce, C., Cortes-Padilla, D., Huntsman, D.G., Miller, M.A., Dueñnas-Gonzalez, A., Alvarado, A., Pérez, V., Gallardo-Rincón, D., Lara-Medina, F. World journal of surgical oncology [electronic resource]. (2005) [Pubmed]
  28. MYC messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma. Grotzer, M.A., Hogarty, M.D., Janss, A.J., Liu, X., Zhao, H., Eggert, A., Sutton, L.N., Rorke, L.B., Brodeur, G.M., Phillips, P.C. Clin. Cancer Res. (2001) [Pubmed]
WikiGenes - Universities