trkc receptor


Summary: A protein-tyrosine kinase receptor that is specific for NEUROTROPHIN 3. It is widely expressed in nervous tissue and may play a role in mediating the effects of NEUROTROPHIN 3 on the proliferation and differentiation of NEURONS.

Top Publications

  1. Averill S, Delcroix J, Michael G, Tomlinson D, Fernyhough P, Priestley J. Nerve growth factor modulates the activation status and fast axonal transport of ERK 1/2 in adult nociceptive neurones. Mol Cell Neurosci. 2001;18:183-96 pubmed
    ..tERK and pERK both undergo fast anterograde and retrograde axonal transport, indicated by accumulation at a sciatic nerve ligature, and NGF reduces the level of retrograde pERK transport. ..
  2. Oakley R, Lefcort F, Clary D, Reichardt L, Prevette D, Oppenheim R, et al. Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the absence of peripheral targets. J Neurosci. 1997;17:4262-74 pubmed
    ..Together, our results indicate that NT3 signaling is both necessary and sufficient for the development of the proprioceptive phenotype, even in the absence of other signals from limb muscle. ..
  3. Nakagawara A. Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett. 2001;169:107-14 pubmed
    ..In this short review, the dynamic role of the Trk family receptors signaling in neural development, neurogenic tumors and other cancers will be discussed. ..
  4. Postigo A, Calella A, Fritzsch B, Knipper M, Katz D, Eilers A, et al. Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons. Genes Dev. 2002;16:633-45 pubmed brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons...
  5. Palko M, Coppola V, Tessarollo L. Evidence for a role of truncated trkC receptor isoforms in mouse development. J Neurosci. 1999;19:775-82 pubmed
    ..Taken together, these data suggest that truncated trkC receptor isoforms may have modulatory functions in development.
  6. Yamauchi J, Chan J, Shooter E. Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway. Proc Natl Acad Sci U S A. 2003;100:14421-6 pubmed
    ..We obtained the same results with Cos-7 cells expressing TrkC. Taken together, these results suggest that neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase signaling pathway. ..
  7. Rudzinski M, Wong T, Saragovi H. Changes in retinal expression of neurotrophins and neurotrophin receptors induced by ocular hypertension. J Neurobiol. 2004;58:341-54 pubmed
    ..A possible rationale for therapeutic intervention with Trk receptor agonists and p75 receptor antagonists is proposed. ..
  8. Liebl D, Tessarollo L, Palko M, Parada L. Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice. J Neurosci. 1997;17:9113-21 pubmed
    ..We suggest that neurotrophins may function in creating early heterogeneity that would enable ganglia to compensate for diverse modality requirements before the period of naturally occurring death. ..
  9. Kramer I, Sigrist M, de Nooij J, Taniuchi I, Jessell T, Arber S. A role for Runx transcription factor signaling in dorsal root ganglion sensory neuron diversification. Neuron. 2006;49:379-93 pubmed
    ..Together, our findings suggest that Runx transcription factor signaling plays a key role in sensory neuron diversification. ..

More Information


  1. Esteban P, Yoon H, Becker J, Dorsey S, Caprari P, Palko M, et al. A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin. J Cell Biol. 2006;173:291-9 pubmed
    ..Thus, our data identify a new signaling pathway elicited by the kinase-deficient TrkCT1 receptor. Moreover, we establish NT3 as an upstream regulator of Arf6. ..
  2. Lamballe F, Smeyne R, Barbacid M. Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system. J Neurosci. 1994;14:14-28 pubmed
    ..The apparent colocalization of trkC transcripts with NT-3 raises the possibility this neurotrophin exerts its trophic effects by a paracrine and/or autocrine mechanism. ..
  3. Hasegawa H, Wang F. Visualizing mechanosensory endings of TrkC-expressing neurons in HS3ST-2-hPLAP mice. J Comp Neurol. 2008;511:543-56 pubmed publisher
    ..Our results revealed the subtype identities of TrkC-positive mechanosensory neurons and demonstrated the usefulness of HS3ST-2 as a genetic marker for these subclasses of neurons. ..
  4. Garner A, Large T. Isoforms of the avian TrkC receptor: a novel kinase insertion dissociates transformation and process outgrowth from survival. Neuron. 1994;13:457-72 pubmed
    b>TrkC receptor isoforms have been identified by cDNA cloning and RT-PCR analysis of embryonic chick brain RNA. An N-terminal truncation motif is missing from the signal sequence and first cysteine cluster of the extracellular domain...
  5. Noga O, Englmann C, Hanf G, Grützkau A, Guhl S, Kunkel G. Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils. Clin Exp Allergy. 2002;32:1348-54 pubmed
    ..Eosinophils express the functionally active receptors TrkA, TrkB and TrkC. Receptor activation stimulates eosinophils. This might be an additional pathway regulating inflammatory responses in allergic reactions. ..
  6. Shi L, Yue J, You Y, Yin B, Gong Y, Xu C, et al. Dok5 is substrate of TrkB and TrkC receptors and involved in neurotrophin induced MAPK activation. Cell Signal. 2006;18:1995-2003 pubmed
    ..In yeast two-hybrid assay, Dok5 can interact with intracellular domain of TrkB and TrkC receptor through its PTB domain, but not with that of TrkA receptor...
  7. Inoue K, Ito K, Osato M, Lee B, Bae S, Ito Y. The transcription factor Runx3 represses the neurotrophin receptor TrkB during lineage commitment of dorsal root ganglion neurons. J Biol Chem. 2007;282:24175-84 pubmed
    ..Taken together, Runx3 determines TrkC positive sensory neuron identities through the transcriptional repression of TrkB when Trk-BTrkC double positive neurons differentiate into TrkC single positive neurons. ..
  8. Tauszig Delamasure S, Yu L, Cabrera J, Bouzas Rodriguez J, Mermet Bouvier C, Guix C, et al. The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm. Proc Natl Acad Sci U S A. 2007;104:13361-6 pubmed
    ..Thus, the death of neurons upon disappearance of NT-3 is not only due to a loss of survival signals but also to the active proapoptotic activity of the unbound TrkC dependence receptor. ..
  9. Nakamura S, Senzaki K, Yoshikawa M, Nishimura M, Inoue K, Ito Y, et al. Dynamic regulation of the expression of neurotrophin receptors by Runx3. Development. 2008;135:1703-11 pubmed publisher
    ..Moreover, we show that the number of TrkA-positive DRG neurons is reduced in Runx3(-/-) mice, as compared with the wild type. These results suggest that Runx3 positively regulates the expression of TrkC and TrkA in DRG neurons. ..
  10. Lamballe F, Klein R, Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991;66:967-79 pubmed
    ..These results indicate that gp145trkC may play an important role in mediating the neurotrophic effects of NT-3. ..
  11. Levanon D, Bettoun D, Harris Cerruti C, Woolf E, Negreanu V, Eilam R, et al. The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. EMBO J. 2002;21:3454-63 pubmed
    ..The data provide new genetic insights into the neurogenesis of DRGs and may help elucidate the molecular mechanisms underlying somatosensory-related ataxia in humans. ..
  12. Ichaso N, Rodriguez R, Martin Zanca D, Gonzalez Sarmiento R. Genomic characterization of the human trkC gene. Oncogene. 1998;17:1871-5 pubmed
    ..5 transcription factors. ..
  13. Tessarollo L, Tsoulfas P, Donovan M, Palko M, Blair Flynn J, Hempstead B, et al. Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis. Proc Natl Acad Sci U S A. 1997;94:14776-81 pubmed
    ..Mice lacking either NT-3 or all trkC receptor isoforms die in the early postnatal period...
  14. Huang E, Wilkinson G, Farinas I, Backus C, Zang K, Wong S, et al. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC. Development. 1999;126:2191-203 pubmed
    ..Therefore, our data provide evidence that NT-3 supports the survival of TrkA-, TrkB- and TrkC-expressing neurons in the trigeminal ganglion by activating directly each of these receptors in vivo. ..
  15. Klein R, Silos Santiago I, Smeyne R, Lira S, Brambilla R, Bryant S, et al. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature. 1994;368:249-51 pubmed
    ..These mice display abnormal movements and postures, indicating that NT3/TrkC-dependent sensor; neurons may play a primary role in proprioception, the sense of position and movement of the limbs. ..
  16. Lamballe F, Tapley P, Barbacid M. trkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities. EMBO J. 1993;12:3083-94 pubmed
    ..Upon interaction with their cognate ligand, NT-3, all three TrkC receptor isoforms become rapidly phosphorylated on tyrosine residues and induce DNA synthesis in quiescent cells...
  17. Menn B, Timsit S, Calothy G, Lamballe F. Differential expression of TrkC catalytic and noncatalytic isoforms suggests that they act independently or in association. J Comp Neurol. 1998;401:47-64 pubmed
  18. Lin J, Saito T, Anderson D, Lance Jones C, Jessell T, Arber S. Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression. Cell. 1998;95:393-407 pubmed
    ..ETS genes may therefore participate in the development of selective sensory-motor circuits in the spinal cord. ..
  19. Tsoulfas P, Soppet D, Escandon E, Tessarollo L, Mendoza Ramirez J, Rosenthal A, et al. The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells. Neuron. 1993;10:975-90 pubmed
    ..This could have important implications in understanding the role of neurotrophins in the development of the vertebrate nervous system. ..
  20. Barnabe Heider F, Miller F. Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J Neurosci. 2003;23:5149-60 pubmed
    ..Thus, neurotrophins made by cortical progenitor cells themselves signal through the TrkB and TrkC receptors to mediate cortical progenitor cell survival and neurogenesis via two distinct downstream signaling pathways. ..
  21. Funfschilling U, Ng Y, Zang K, Miyazaki J, Reichardt L, Rice F. TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells. J Comp Neurol. 2004;480:392-414 pubmed
    ..Many types of nonneuronal cells affiliated with hair follicles and blood vessels also express TrkC-reporter but lack immunodetectable TrkC. ..
  22. McEvilly R, Erkman L, Luo L, Sawchenko P, Ryan A, Rosenfeld M. Requirement for Brn-3.0 in differentiation and survival of sensory and motor neurons. Nature. 1996;384:574-7 pubmed
    ..Deletion of Brn-3.0 also alters either differentiation, migration or survival of specific central neuronal populations. ..
  23. Bartkowska K, Paquin A, Gauthier A, Kaplan D, Miller F. Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development. Development. 2007;134:4369-80 pubmed
  24. Huang E, Zang K, Schmidt A, Saulys A, Xiang M, Reichardt L. POU domain factor Brn-3a controls the differentiation and survival of trigeminal neurons by regulating Trk receptor expression. Development. 1999;126:2869-82 pubmed
    ..In conclusion, our data indicate the specific functions of Brn-3a in controlling the survival and differentiation of trigeminal neurons by regulating expression of each of the three Trk receptors. ..
  25. Baker K, Nakashima S, Hagg T. Dorsal column sensory axons lack TrkC and are not rescued by local neurotrophin-3 infusions following spinal cord contusion in adult rats. Exp Neurol. 2007;205:82-91 pubmed
    ..Together with published results, our data suggest that NT-3 is a peripherally--but not centrally--derived neurotrophic factor for sensory neurons. ..
  26. Yang M, Cagle M, Honig M. Identification of cerebellin2 in chick and its preferential expression by subsets of developing sensory neurons and their targets in the dorsal horn. J Comp Neurol. 2010;518:2818-40 pubmed publisher
  27. Guillemard V, Ivanisevic L, Garcia A, Scholten V, Lazo O, Bronfman F, et al. An agonistic mAb directed to the TrkC receptor juxtamembrane region defines a trophic hot spot and interactions with p75 coreceptors. Dev Neurobiol. 2010;70:150-64 pubmed publisher
    ..mAb 2B7 defines a previously unknown neurotrophin receptor functional hot spot; that exclusively generates survival signals; that can be activated by non-dimeric ligands; and potentially unmasks a site for p75-TrkC interactions. ..
  28. Yang B, Shan L, Song W, Xiao Z, Shi L, Yuan H. Copolymer-1 immunization reduces damage in retinal ganglion cells under high intraocular pressure through altering the expression of retinal neurotrophins. J Ocul Pharmacol Ther. 2010;26:11-9 pubmed publisher
    ..Moreover, the expression of the COP-1 receptor, TrkC, increased accordingly. COP-1 immunization might increase NT-3 expression by some unknown mechanism in high IOP rats and the change may be related to COP-1 therapeutic intervention. ..
  29. Nassenstein C, Möhring U, Luttmann W, Virchow J, Braun A. Differential expression of the neurotrophin receptors p75NTR, TrkA, TrkB and TrkC in human peripheral blood mononuclear cells. Exp Toxicol Pathol. 2006;57 Suppl 2:55-63 pubmed
    ..Our results show that each of the receptors has an individual expression pattern in diverse immune cell subtypes. However, there were no differences in neurotrophin receptor expression in healthy controls and patients with allergies. ..
  30. Stephan H, Zakrzewski J, Bölöni R, Grasemann C, Lohmann D, Eggert A. Neurotrophin receptor expression in human primary retinoblastomas and retinoblastoma cell lines. Pediatr Blood Cancer. 2008;50:218-22 pubmed
    ..Our findings suggest a role for neurotrophin signaling in the biology of retinoblastoma. General Trk inhibitors are effective in decreasing growth rates of retinoblastoma cells in vitro, and should be evaluated in in vivo studies. ..
  31. Ryden M, Ibanez C. Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC. J Biol Chem. 1996;271:5623-7 pubmed
  32. Grotzer M, von Hoff K, von Bueren A, Shalaby T, Hartmann W, Warmuth Metz M, et al. Which clinical and biological tumor markers proved predictive in the prospective multicenter trial HIT'91--implications for investigating childhood medulloblastoma. Klin Padiatr. 2007;219:312-7 pubmed
    ..Upon prospective validation of cut-off levels, this may lead to better risk-based stratification systems for children with medulloblastoma. ..
  33. Light K, Brown D, Newton B, Belcher S, Kane C. Ethanol-induced alterations of neurotrophin receptor expression on Purkinje cells in the neonatal rat cerebellum. Brain Res. 2002;924:71-81 pubmed
    ..These results suggest that ethanol may induce loss of Purkinje cells by alteration of neurotrophic regulation at this critical stage. ..
  34. Ohta T, Watanabe T, Katayama Y, Kurihara J, Yoshino A, Nishimoto H, et al. TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomas. Neuropathology. 2006;26:170-7 pubmed
  35. Rubio N, Abad Rodriguez J. Adenovirus vector-directed expression of the neurotrophin-3 receptor (TrkC) in mouse astrocytes. J Neurovirol. 2001;7:72-81 pubmed
    ..These results demonstrate that our AdTrkC vector efficiently mediates the expression of high-levels of biologically active NT-3 receptors. ..
  36. Wyatt S, Pinon L, Ernfors P, Davies A. Sympathetic neuron survival and TrkA expression in NT3-deficient mouse embryos. EMBO J. 1997;16:3115-23 pubmed
    ..The expression of transcripts encoding catalytic TrkC is negligible at this stage, suggesting that NT3 acts mainly via TrkA. ..
  37. Ricci A, Graziano P, Mariotta S, Cardillo G, Sposato B, Terzano C, et al. Neurotrophin system expression in human pulmonary carcinoid tumors. Growth Factors. 2005;23:303-12 pubmed
    ..Contrarily to the BDNF/TrkB, expression of the NGF/TrkA signaling may overcome aggressiveness of carcinoid cells. NTs may be useful as markers in the clinic. ..
  38. Kong B, Liu Y, Lu X. Decreased expression of neurotrophic tyrosine receptor kinase 3 is associated with the outflow tract defect of human tetralogy of Fallot. Chin Med J (Engl). 2009;122:153-7 pubmed
    ..Insufficient expression of NTRK3 is associated with the outflow tract defect of human tetralogy of Fallot and may contribute to the progression of this defect. ..
  39. Hempstead B, Salzer J. Neurobiology. A glial spin on neurotrophins. Science. 2002;298:1184-6 pubmed
  40. Sheng W, Hisaoka M, Okamoto S, Tanaka A, Meis Kindblom J, Kindblom L, et al. Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues. Am J Clin Pathol. 2001;115:348-55 pubmed
  41. Vicario Abejón C, Collin C, Tsoulfas P, McKay R. Hippocampal stem cells differentiate into excitatory and inhibitory neurons. Eur J Neurosci. 2000;12:677-88 pubmed
    ..These data show that stem cells can be used to study mechanisms of excitation and inhibition in the nervous system. ..
  42. Ivanisevic L, Banerjee K, Saragovi H. Differential cross-regulation of TrkA and TrkC tyrosine kinase receptors with p75. Oncogene. 2003;22:5677-85 pubmed
    ..Therefore, a complex homeostasis of p75-selective and Trk-selective signals may determine the fate of cells expressing both receptors. ..
  43. Matsuo S, Ichikawa H, Silos Santiago I, Arends J, Henderson T, Kiyomiya K, et al. Proprioceptive afferents survive in the masseter muscle of trkC knockout mice. Neuroscience. 2000;95:209-16 pubmed
    ..It is likely that one or more other neurotrophin receptors expressed in mesencephalic trigeminal proprioceptive neurons of trkC knockout mice compensate for the lack of normal neurotrophin-3 signaling through trkC. ..
  44. Huber H, Eggert A, Janss A, Wiewrodt R, Zhao H, Sutton L, et al. Angiogenic profile of childhood primitive neuroectodermal brain tumours/medulloblastomas. Eur J Cancer. 2001;37:2064-72 pubmed
    ..This suggests that anti-angiogenesis approaches targeting VEGF alone may be insufficient in PNET/MB. ..
  45. Avivi C, Goldstein R. Differing patterns of neurotrophin-receptor expressing neurons allow distinction of the transient Frorieps' ganglia from normal DRG before morphological differences appear. Brain Res Dev Brain Res. 2003;145:49-59 pubmed
  46. Checa N, Canals J, Gratacos E, Alberch J. TrkB and TrkC are differentially regulated by excitotoxicity during development of the basal ganglia. Exp Neurol. 2001;172:282-92 pubmed
    ..These results demonstrate that the endogenous response to excitotoxicity includes transneuronal regulation of neurotrophin receptors, which is specific for each nucleus and depends on the developmental stage. ..
  47. Marchetti D, Mrak R, Paulsen D, Sinnappah Kang N. Neurotrophin receptors and heparanase: a functional axis in human medulloblastoma invasion. J Exp Clin Cancer Res. 2007;26:5-23 pubmed
    ..Taken together, our data provide evidence that HPSE functionality, in a context linked to TrkC and p75NTR activation, may play critical roles in medulloblastoma tumor invasion and progression. ..
  48. Pinon L, Minichiello L, Klein R, Davies A. Timing of neuronal death in trkA, trkB and trkC mutant embryos reveals developmental changes in sensory neuron dependence on Trk signalling. Development. 1996;122:3255-61 pubmed
    ..These results demonstrate that TrkB signalling is required for the in vivo survival of many trigeminal neurons during the early stages of target field innervation before they become NGF-dependent. ..
  49. Fritzsch B, Barbacid M, Silos Santiago I. The combined effects of trkB and trkC mutations on the innervation of the inner ear. Int J Dev Neurosci. 1998;16:493-505 pubmed
  50. Otal R, MARTINEZ A, Soriano E. Lack of TrkB and TrkC signaling alters the synaptogenesis and maturation of mossy fiber terminals in the hippocampus. Cell Tissue Res. 2005;319:349-58 pubmed
    ..Our results therefore reveal that TrkB and TrkC signaling is required for the maturation of granule cell axons. ..
  51. Arnold S, Facer P, Yiangou Y, Chen M, Plumpton C, Tate S, et al. Decreased potassium channel IK1 and its regulator neurotrophin-3 (NT-3) in inflamed human bowel. Neuroreport. 2003;14:191-5 pubmed
    ..Our findings may explain the diarrhoea and colicky abdominal pain produced by inflammatory bowel disease, and by IK1-blocking pyridine drugs prescribed for neuromuscular disorders. ..
  52. Bianco J, Perry C, Harkin D, Mackay Sim A, Feron F. Neurotrophin 3 promotes purification and proliferation of olfactory ensheathing cells from human nose. Glia. 2004;45:111-23 pubmed
    ..This technique opens the door for clinical trials in which nasal ensheathing cells will be autotransplanted in humans suffering from nerve injury. ..
  53. Ketterer K, Rao S, Friess H, Weiss J, Buchler M, Korc M. Reverse transcription-PCR analysis of laser-captured cells points to potential paracrine and autocrine actions of neurotrophins in pancreatic cancer. Clin Cancer Res. 2003;9:5127-36 pubmed
    ..Thus, our findings provide additional evidence that blocking NT actions may have a therapeutic potential in PDAC. ..