trka receptor


Summary: A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.

Top Publications

  1. Julio Pieper M, Lozada P, Tapia V, Vega M, Miranda C, Vantman D, et al. Nerve growth factor induces vascular endothelial growth factor expression in granulosa cells via a trkA receptor/mitogen-activated protein kinase-extracellularly regulated kinase 2-dependent pathway. J Clin Endocrinol Metab. 2009;94:3065-71 pubmed publisher
    ..NGF promotes VEGF production in cultured hGCs. Blockade of trkA receptor tyrosine kinase activity blocks this effect...
  2. Sundara Rajan S, Vu T. Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells. Nano Lett. 2006;6:2049-59 pubmed
    ..QDs are contained in microtubule-associated vesicles and possess transport properties that reflect TrkA receptor dynamics...
  3. Yuan Y, Fu C, Chen H, Wang X, Deng W, Huang B. The Ran binding protein RanBPM interacts with TrkA receptor. Neurosci Lett. 2006;407:26-31 pubmed
    ..These data suggested that RanBPM could participate in neurotrophin-mediated gene transcription and expression by its binding to TrkA. ..
  4. Sobottka B, Reinhardt D, Brockhaus M, Jacobsen H, Metzger F. ProNGF inhibits NGF-mediated TrkA activation in PC12 cells. J Neurochem. 2008;107:1294-303 pubmed publisher
    ..In this study, we show that proNGF can mediate TrkA receptor signaling directly, yet in the manner of a partial agonist with a lower maximum activity than NGF...
  5. El Hashim A, Jaffal S. Nerve growth factor enhances cough and airway obstruction via TrkA receptor- and TRPV1-dependent mechanisms. Thorax. 2009;64:791-7 pubmed publisher
    ..Pretreatment with the TrkA receptor antagonist, K252a, or the TRPV1 antagonist, iodoresiniferatoxin, significantly inhibited the NGF-enhanced ..
  6. Lei L, Zhou J, Lin L, Parada L. Brn3a and Klf7 cooperate to control TrkA expression in sensory neurons. Dev Biol. 2006;300:758-69 pubmed
    ..Thus, cooperation between these two transcription factors is required for endogenous TrkA gene expression and the survival of nociceptive sensory neurons. ..
  7. Urra S, Escudero C, Ramos P, Lisbona F, Allende E, Covarrubias P, et al. TrkA receptor activation by nerve growth factor induces shedding of the p75 neurotrophin receptor followed by endosomal gamma-secretase-mediated release of the p75 intracellular domain. J Biol Chem. 2007;282:7606-15 pubmed
    ..We demonstrate that activation of the TrkA receptor upon binding of nerve growth factor (NGF) regulates the metalloprotease-mediated shedding of p75 leaving a ..
  8. Rajagopal R, Chao M. A role for Fyn in Trk receptor transactivation by G-protein-coupled receptor signaling. Mol Cell Neurosci. 2006;33:36-46 pubmed
    ..These results indicate that Fyn is activated by GPCR stimulation and is responsible for transactivation of Trk receptors on intracellular membranes. ..
  9. Auer Grumbach M, Mauko B, Auer Grumbach P, Pieber T. Molecular genetics of hereditary sensory neuropathies. Neuromolecular Med. 2006;8:147-58 pubmed
    ..Nevertheless, it remains unclear how mutations in the known genes lead to the phenotype of HSN. In this review, we summarize the recent progress of the molecular genetics of the HSN and the implicated genes. ..

More Information


  1. Micera A, Lambiase A, Stampachiacchiere B, Bonini S, Bonini S, Levi Schaffer F. Nerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two receptors one fate. Cytokine Growth Factor Rev. 2007;18:245-56 pubmed
    ..In summary, these novel findings on the potential pro-healing capacity of NGF might open new possibilities for this growth factor in modulating the healing processes in several pathological conditions. ..
  2. Hansen K, Wagner B, Hamel W, Schweizer M, Haag F, Westphal M, et al. Autophagic cell death induced by TrkA receptor activation in human glioblastoma cells. J Neurochem. 2007;103:259-75 pubmed
    ..Our findings suggest that TrkA activation in human glioblastomas might be beneficial therapeutically, especially as several of the currently used chemotherapeutics also induce autophagic cell death. ..
  3. Meyer J, Rhein M, Schiedlmeier B, Kustikova O, Rudolph C, Kamino K, et al. Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, deltaTrkA. Leukemia. 2007;21:2171-80 pubmed
  4. Hisata S, Sakisaka T, Baba T, Yamada T, Aoki K, Matsuda M, et al. Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. J Cell Biol. 2007;178:843-60 pubmed
    ..scaffolding molecule and ankyrin repeat-rich membrane spanning protein which interacts directly with the TrkA receptor. At late endosomes, the complex induces sustained activation of Rap1 and ERK, resulting in neurite outgrowth...
  5. Jang S, Okada M, Sayeed I, Xiao G, Stein D, Jin P, et al. Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death. Proc Natl Acad Sci U S A. 2007;104:16329-34 pubmed
    Nerve growth factor (NGF) binds to TrkA receptor and triggers activation of numerous signaling cascades, which play critical roles in neuronal plasticity, survival, and neurite outgrowth...
  6. de Melo Jorge M, PereiraPerrin M. The Chagas' disease parasite Trypanosoma cruzi exploits nerve growth factor receptor TrkA to infect mammalian hosts. Cell Host Microbe. 2007;1:251-61 pubmed
    ..Thus, TrkA, the nerve growth factor receptor commonly associated with neural survival and protection, may also underlie clinical progression of an important human parasitic disease. ..
  7. Boutilier J, Ceni C, Pagdala P, Forgie A, Neet K, Barker P. Proneurotrophins require endocytosis and intracellular proteolysis to induce TrkA activation. J Biol Chem. 2008;283:12709-16 pubmed publisher
    ..However, endocytosis and cleavage of proneurotrophins produce processed forms of neurotrophins that are capable of inducing Trk activation. ..
  8. Tuysuz B, Bayrakli F, DiLuna M, Bilguvar K, Bayri Y, Yalcinkaya C, et al. Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population. Neurogenetics. 2008;9:119-25 pubmed publisher
    ..This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population...
  9. Sun Y, Dykes I, Liang X, Eng S, Evans S, Turner E. A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nat Neurosci. 2008;11:1283-93 pubmed publisher
    ..Together these results establish a central role for Islet1 in the transition from sensory neurogenesis to subtype specification. ..
  10. Kilic S, Ozturk R, Sarisozen B, Rotthier A, Baets J, Timmerman V. Humoral immunodeficiency in congenital insensitivity to pain with anhidrosis. Neurogenetics. 2009;10:161-5 pubmed publisher
    ..The implication of the immune system of the reported patient broadens the clinical phenotype associated with NTRK1 mutations. ..
  11. Valdez G, Philippidou P, Rosenbaum J, Akmentin W, Shao Y, Halegoua S. Trk-signaling endosomes are generated by Rac-dependent macroendocytosis. Proc Natl Acad Sci U S A. 2007;104:12270-5 pubmed
    ..Thus, a population of stable Trk endosomes, formed by specialized macroendocytosis in neurons, provides a privileged endosome-based system for propagation of signals to the nucleus. ..
  12. Ivanisevic L, Zheng W, Woo S, Neet K, Saragovi H. TrkA receptor "hot spots" for binding of NT-3 as a heterologous ligand. J Biol Chem. 2007;282:16754-63 pubmed
    ..This study demonstrates that Trk signaling is more complex than previously thought because it involves several receptor subdomains and hot spots. ..
  13. Abe Y, Akeda K, An H, Aoki Y, Pichika R, Muehleman C, et al. Proinflammatory cytokines stimulate the expression of nerve growth factor by human intervertebral disc cells. Spine (Phila Pa 1976). 2007;32:635-42 pubmed
  14. Deppmann C, Mihalas S, Sharma N, Lonze B, Niebur E, Ginty D. A model for neuronal competition during development. Science. 2008;320:369-73 pubmed publisher
    ..We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. ..
  15. Geetha T, Wooten M. TrkA receptor endolysosomal degradation is both ubiquitin and proteasome dependent. Traffic. 2008;9:1146-56 pubmed publisher
    ..The trafficking of the polyubiquitin-deficient TrkA receptor mutant K485R was impaired and likewise failed to degrade revealing that the receptor escapes degradation...
  16. Li C, MacDonald J, Hryciw T, Meakin S. Nerve growth factor activation of the TrkA receptor induces cell death, by macropinocytosis, in medulloblastoma Daoy cells. J Neurochem. 2010;112:882-99 pubmed publisher
    Ectopic expression of the TrkA receptor tyrosine kinase in tumors of the nervous system can mediate nerve growth factor (NGF)-dependent cell death by apoptosis and /or autophagy...
  17. Zarate J, Goicoechea E, Pascual J, Echevarria E, Guillén M. A study of the toxic effect of oxidized sunflower oil containing 4-hydroperoxy-2-nonenal and 4-hydroxy-2-nonenal on cortical TrkA receptor expression in rats. Nutr Neurosci. 2009;12:249-59 pubmed publisher
    ..A significant decrease in the number of neural cells positively immunostained for TrkA receptor was detected in the frontal cortex of the experimental group, with respect to controls, suggesting both ..
  18. Harel L, Costa B, Tcherpakov M, Zapatka M, Oberthuer A, Hansford L, et al. CCM2 mediates death signaling by the TrkA receptor tyrosine kinase. Neuron. 2009;63:585-91 pubmed publisher
    The TrkA receptor tyrosine kinase is crucial for differentiation and survival of nerve-growth-factor-dependent neurons. Paradoxically, TrkA also induces cell death in pediatric tumor cells of neural origin, via an unknown mechanism...
  19. Yoshikawa M, Senzaki K, Yokomizo T, Takahashi S, Ozaki S, Shiga T. Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons. Dev Biol. 2007;303:663-74 pubmed
    ..Our results suggest that Runx1 is involved in the cell fate specification of cutaneous neurons, as well as their projections to central and peripheral targets. ..
  20. Lee X, Yang Z, Shao Z, Rosenberg S, Levesque M, Pepinsky R, et al. NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination. J Neurosci. 2007;27:220-5 pubmed
    ..The implications of these results relate specifically to the development of potential therapeutics targeting extrinsic growth factors that may regulate the axonal expression of modulators of oligodendrocyte development. ..
  21. Micera A, Lambiase A, Puxeddu I, Aloe L, Stampachiacchiere B, Levi Schaffer F, et al. Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing. Exp Eye Res. 2006;83:747-57 pubmed
    ..To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing. ..
  22. Verhoeven K, Timmerman V, Mauko B, Pieber T, De Jonghe P, Auer Grumbach M. Recent advances in hereditary sensory and autonomic neuropathies. Curr Opin Neurol. 2006;19:474-80 pubmed
    ..This review summarizes the genetic advances of hereditary sensory neuropathies and hereditary sensory and autonomic neuropathies, and provides information on phenotype-genotype correlation and on possible underlying pathomechanisms...
  23. Conti G, Gale K, Kondratyev A. Immunohistochemical evaluation of the protein expression of nerve growth factor and its TrkA receptor in rat limbic regions following electroshock seizures. Neurosci Res. 2009;65:201-9 pubmed publisher
    ..The neuroprotective action of NGF is mediated by the TrkA receptor. This study determined whether repeated ECS exposure increased TrkA and NGF protein levels...
  24. Coassin M, Lambiase A, Sposato V, Micera A, Bonini S, Aloe L. Retinal p75 and bax overexpression is associated with retinal ganglion cells apoptosis in a rat model of glaucoma. Graefes Arch Clin Exp Ophthalmol. 2008;246:1743-9 pubmed publisher
    ..The failure of NGF trophic support might be associated with the progressive up-regulation of p75(NTR) in relation to trkA(NGFR). ..
  25. de Pablo Y, Perez Garcia M, Georgieva M, Sanchis D, Lindqvist N, Soler R, et al. Tyr-701 is a new regulatory site for neurotrophin receptor TrkA trafficking and function. J Neurochem. 2008;104:124-39 pubmed publisher
    ..This is the first evidence that a Tyr residue can simultaneously regulate TrkA receptor trafficking and activity.
  26. Sun X, Xu X, Wang F, Zhang X, Ho P, Liu H, et al. Nerve growth factor helps protect retina in experimental retinal detachment. Ophthalmologica. 2008;222:58-61 pubmed
    ..Intravitreal injection of exogenous NGF can protect retinal cells from degeneration in experimental RD. It may exert its protective action by preventing the apoptosis of retinal cells after RD. ..
  27. Valderrama X, Misra V. Novel Brn3a cis-acting sequences mediate transcription of human trkA in neurons. J Neurochem. 2008;105:425-35 pubmed
    ..In addition, Brn3a increased levels of endogenous trkA transcripts in PC12 cells and initiated trkA expression in medulloblastoma cells, which normally do not express trkA. ..
  28. El Zein N, Badran B, Sariban E. The neuropeptide pituitary adenylate cyclase activating protein stimulates human monocytes by transactivation of the Trk/NGF pathway. Cell Signal. 2007;19:152-62 pubmed
    ..polypeptide (PACAP) acting through the GPCR VPAC-1 exerts trophic effects by transactivating the RTK TrkA receptor for the nerve growth factor (NGF). Both PACAP and NGF have pro-inflammatory activities on monocytes...
  29. Du Y, Fischer T, Clinton Luke P, Lercher L, Dreyfus C. Distinct effects of p75 in mediating actions of neurotrophins on basal forebrain oligodendrocytes. Mol Cell Neurosci. 2006;31:366-75 pubmed
    ..On the other hand, K252a, an inhibitor of trk receptors, abolished the effects of the neurotrophins, including BDNF. All neurotrophins activated their respective trk receptors. ..
  30. Rihl M, Kruithof E, Barthel C, De Keyser F, Veys E, Zeidler H, et al. Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment. Ann Rheum Dis. 2005;64:1542-9 pubmed
    ..NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes. ..
  31. Marmigere F, Montelius A, Wegner M, Groner Y, Reichardt L, Ernfors P. The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons. Nat Neurosci. 2006;9:180-7 pubmed
    ..Our data show that Runx1 directs, in a context-dependent manner, key aspects of the establishment of the TrkA(+) nociceptive subclass of neurons. ..
  32. Chen C, Broom D, Liu Y, de Nooij J, Li Z, Cen C, et al. Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain. Neuron. 2006;49:365-77 pubmed
    ..Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a finding with implications for pain therapy. ..
  33. Micera A, Puxeddu I, Lambiase A, Antonelli A, Bonini S, Aloe L, et al. The pro-fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor-beta. Clin Exp Allergy. 2005;35:650-6 pubmed
    ..Our findings indicate that NGF, via TGF-beta induction, is likely to be involved in the healing or fibrotic processes occurring in conjunctiva during some pathological conditions. ..
  34. Valdez G, Akmentin W, Philippidou P, Kuruvilla R, Ginty D, Halegoua S. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors. J Neurosci. 2005;25:5236-47 pubmed
    ..Pincher is the first distinguishing molecular component of a novel mechanistic pathway for endosomal signaling in neurons. ..
  35. Pierotti M, Greco A. Oncogenic rearrangements of the NTRK1/NGF receptor. Cancer Lett. 2006;232:90-8 pubmed
    ..The modalities of their activation, their mechanism of action, the contribution of activating sequences, and the molecular mechanisms underlying their generation will be discussed. ..
  36. Verpoorten N, Claeys K, Deprez L, Jacobs A, Van Gerwen V, Lagae L, et al. Novel frameshift and splice site mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with hereditary sensory neuropathy type IV. Neuromuscul Disord. 2006;16:19-25 pubmed
    ..NTRK1 mutations are only rarely reported in the European population. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with HSAN IV...
  37. Schramm A, Schulte J, Astrahantseff K, Apostolov O, Limpt V, Sieverts H, et al. Biological effects of TrkA and TrkB receptor signaling in neuroblastoma. Cancer Lett. 2005;228:143-53 pubmed
    ..This short review discusses recent data on the biological roles of TrkA and TrkB signaling in neuroblastoma. ..
  38. Dollé J, Rezvan A, Allen F, Lazarovici P, Lelkes P. Nerve growth factor-induced migration of endothelial cells. J Pharmacol Exp Ther. 2005;315:1220-7 pubmed
    ..NGF-mediated stimulation of HAEC migration was completely blocked by the NGF/TrkA receptor antagonist K252a [(8R*,9S*,11S*)-(/)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,-..
  39. Saxena S, Howe C, Cosgaya J, Steiner P, Hirling H, Chan J, et al. Differential endocytic sorting of p75NTR and TrkA in response to NGF: a role for late endosomes in TrkA trafficking. Mol Cell Neurosci. 2005;28:571-87 pubmed
    ..Disrupting p75NTR recycling diminished TrkA activation in response to low concentrations of NGF, demonstrating a functional role for the recycling of p75NTR. ..
  40. Liu H, MacDonald J, Hryciw T, Li C, Meakin S. Human tumorous imaginal disc 1 (TID1) associates with Trk receptor tyrosine kinases and regulates neurite outgrowth in nnr5-TrkA cells. J Biol Chem. 2005;280:19461-71 pubmed
    ..These data provide the first evidence that TID1 is a novel intracellular adaptor that interacts with the Trk receptor tyrosine kinases in an activity-dependent manner to facilitate Trk-dependent intracellular signaling. ..
  41. Lenzi L, Coassin M, Lambiase A, Bonini S, Amendola T, Aloe L. Effect of exogenous administration of nerve growth factor in the retina of rats with inherited retinitis pigmentosa. Vision Res. 2005;45:1491-500 pubmed
    ..This suggests that NGF has an effect on RCS rat retina, probably also through the stimulation of other biological mediators produced and released in the retina. ..
  42. Benito Gutiérrez E, Garcia Fernandez J, Comella J. Origin and evolution of the Trk family of neurotrophic receptors. Mol Cell Neurosci. 2006;31:179-92 pubmed
    ..It is suggestive to propose that subtle protein mutations, gene duplications, and co-options in particular territories of a primitive Nt/Trk system were instrumental to the development of a complex vertebrate nervous system. ..
  43. Schreiber R, Levy J, Loewenthal N, Pinsk V, Hershkovitz E. Decreased first phase insulin response in children with congenital insensitivity to pain with anhidrosis. J Pediatr Endocrinol Metab. 2005;18:873-7 pubmed
    ..Additional studies on the clinical significance of NGF-TrkA effects on insulin secretion are required...
  44. Chao M, Rajagopal R, Lee F. Neurotrophin signalling in health and disease. Clin Sci (Lond). 2006;110:167-73 pubmed
    ..In this review, we consider the signalling pathways activated by neurotrophins in both health and disease states. ..
  45. Arevalo J, Pereira D, Yano H, Teng K, Chao M. Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation. J Biol Chem. 2006;281:1001-7 pubmed
    ..Therefore, Trk receptor signaling involves an inducible switch mechanism through an unconventional substrate that distinguishes neurotrophin action from other growth factor receptors. ..
  46. Saxena S, Bucci C, Weis J, Kruttgen A. The small GTPase Rab7 controls the endosomal trafficking and neuritogenic signaling of the nerve growth factor receptor TrkA. J Neurosci. 2005;25:10930-40 pubmed
    Nerve growth factor (NGF) and its TrkA receptor exert important bioactivities on neuronal cells such as promoting survival and neurite outgrowth...
  47. Chuenkova M, PereiraPerrin M. A synthetic peptide modeled on PDNF, Chagas' disease parasite neurotrophic factor, promotes survival and differentiation of neuronal cells through TrkA receptor. Biochemistry. 2005;44:15685-94 pubmed
  48. Wang G, Tokushige N, Markham R, Fraser I. Rich innervation of deep infiltrating endometriosis. Hum Reprod. 2009;24:827-34 pubmed publisher
    ..The rich innervation of DIE may help to explain why patients with this type of lesion have severe pelvic pain. ..
  49. Weier H, Kwan J, Lu C, Ito Y, Wang M, Baumgartner A, et al. Kinase expression and chromosomal rearrangements in papillary thyroid cancer tissues: investigations at the molecular and microscopic levels. J Physiol Pharmacol. 2009;60 Suppl 4:47-55 pubmed
    ..Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention. ..
  50. Pagano N, Wong E, Breiding T, Liu H, Wilbuer A, Bregman H, et al. From imide to lactam metallo-pyridocarbazoles: distinct scaffolds for the design of selective protein kinase inhibitors. J Org Chem. 2009;74:8997-9009 pubmed publisher
  51. Munoz M, Rodriguez A, Diez C, Caamano J, Fernandez Sanchez M, Perez Gomez A, et al. Tyrosine kinase A, C and fibroblast growth factor-2 receptors in bovine embryos cultured in vitro. Theriogenology. 2009;71:1005-10 pubmed publisher
    ..This work may help to design future research with neurotrophins in bovine embryo culture and embryonic stem cells. ..
  52. Santos S, Verveer P, Bastiaens P. Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nat Cell Biol. 2007;9:324-30 pubmed
    ..These results show that growth factor context determines the topology of the MAPK signalling network and that the resulting dynamics govern cell fate. ..
  53. Liu J, Lamb D, Chou M, Liu Y, Li G. Nerve growth factor-mediated neurite outgrowth via regulation of Rab5. Mol Biol Cell. 2007;18:1375-84 pubmed
    ..Thus, NGF signaling down-regulates Rab5 activity via RabGAP5 to facilitate neurite outgrowth and differentiation. ..