trka receptor

Summary

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. ncbi Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF
    D R Kaplan
    Eukaryotic Signal Transduction Group, NCI Frederick Cancer Research and Development Center, Maryland 21701
    Nature 350:158-60. 1991
  2. ncbi NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals
    Jean Dominique Delcroix
    Department of Neurology and Neurological Sciences, Stanford University, Stanford 94305, USA
    Neuron 39:69-84. 2003
  3. ncbi CCM2 mediates death signaling by the TrkA receptor tyrosine kinase
    Liraz Harel
    Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel
    Neuron 63:585-91. 2009
  4. ncbi Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing
    Alessandra Micera
    CIR Laboratory of Ophthalmology, University Campus Bio Medico and G B Bietti, Foundation, Via Emilio Longoni 83, 00155 Rome, Italy
    Exp Eye Res 83:747-57. 2006
  5. ncbi The trk proto-oncogene encodes a receptor for nerve growth factor
    R Klein
    Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
    Cell 65:189-97. 1991
  6. pmc A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs
    Yunfu Sun
    Department of Medicine, University of California San Diego, La Jolla, California 93093, USA
    Nat Neurosci 11:1283-93. 2008
  7. ncbi TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma
    Antonella Tacconelli
    Department of Experimental Medicine, University of L Aquila, Via Vetoio, Coppito 2, 67100 L Aquila, Italy
    Cancer Cell 6:347-60. 2004
  8. ncbi Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene
    R J Smeyne
    Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
    Nature 368:246-9. 1994
  9. ncbi NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway
    C L Howe
    Department of Neurology, Stanford University Medical Center, 1201 Welch Road, MSLS P211, Stanford, CA 94305, USA
    Neuron 32:801-14. 2001
  10. pmc The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death
    S X Bamji
    Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4
    J Cell Biol 140:911-23. 1998

Detail Information

Publications226 found, 100 shown here

  1. ncbi Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF
    D R Kaplan
    Eukaryotic Signal Transduction Group, NCI Frederick Cancer Research and Development Center, Maryland 21701
    Nature 350:158-60. 1991
    ..Activation of the trk tyrosine kinase receptor provides a possible mechanism for signal transduction by NGF...
  2. ncbi NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals
    Jean Dominique Delcroix
    Department of Neurology and Neurological Sciences, Stanford University, Stanford 94305, USA
    Neuron 39:69-84. 2003
    ..Our results are evidence that signaling endosomes, with the characteristics of early endosomes, convey NGF signals from the target of nociceptive neurons to their cell bodies...
  3. ncbi CCM2 mediates death signaling by the TrkA receptor tyrosine kinase
    Liraz Harel
    Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel
    Neuron 63:585-91. 2009
    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...
  4. ncbi Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing
    Alessandra Micera
    CIR Laboratory of Ophthalmology, University Campus Bio Medico and G B Bietti, Foundation, Via Emilio Longoni 83, 00155 Rome, Italy
    Exp Eye Res 83:747-57. 2006
    ..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...
  5. ncbi The trk proto-oncogene encodes a receptor for nerve growth factor
    R Klein
    Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
    Cell 65:189-97. 1991
    ..These results indicate that gp140trk is a functional NGF receptor that mediates at least some of the signal transduction processes initiated by this neurotrophic factor...
  6. pmc A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs
    Yunfu Sun
    Department of Medicine, University of California San Diego, La Jolla, California 93093, USA
    Nat Neurosci 11:1283-93. 2008
    ..Together these results establish a central role for Islet1 in the transition from sensory neurogenesis to subtype specification...
  7. ncbi TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma
    Antonella Tacconelli
    Department of Experimental Medicine, University of L Aquila, Via Vetoio, Coppito 2, 67100 L Aquila, Italy
    Cancer Cell 6:347-60. 2004
    ....
  8. ncbi Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene
    R J Smeyne
    Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
    Nature 368:246-9. 1994
    ..These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems...
  9. ncbi NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway
    C L Howe
    Department of Neurology, Stanford University Medical Center, 1201 Welch Road, MSLS P211, Stanford, CA 94305, USA
    Neuron 32:801-14. 2001
    ..Our results point to the existence of a population of signaling endosomes derived from clathrin-coated membranes in NGF-treated cells...
  10. pmc The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death
    S X Bamji
    Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4
    J Cell Biol 140:911-23. 1998
    ..Together, these data indicate that p75NTR can signal to mediate apoptosis, and that this mechanism is essential for naturally occurring sympathetic neuron death...
  11. ncbi Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor
    C Wiesmann
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    Nature 401:184-8. 1999
    ....
  12. ncbi Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways
    S Descamps
    Equipe Facteurs de Croissance, , , 59655 Villeneuve d' ASCQ France
    J Biol Chem 276:17864-70. 2001
    ..These data show that two distinct signaling pathways are required for NGF activity and confirm the roles played by p75(NTR) and NF-kappaB in the activation of the survival pathway in breast cancer cells...
  13. ncbi Biological effects of TrkA and TrkB receptor signaling in neuroblastoma
    Alexander Schramm
    Division of Hematology Oncology and Endocrinology, University Children s Hospital of Essen, Hufelandstrasse 55, 45122 Essen, Germany
    Cancer Lett 228:143-53. 2005
    ..This short review discusses recent data on the biological roles of TrkA and TrkB signaling in neuroblastoma...
  14. ncbi A novel p75 neurotrophin receptor-related protein, NRH2, regulates nerve growth factor binding to the TrkA receptor
    Simon S Murray
    Skirball Institute of Bimolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    J Neurosci 24:2742-9. 2004
    ..Coexpression of NRH2 with TrkA receptors resulted in the formation of high-affinity binding sites for NGF. These results indicate that a transmembrane protein related to p75NTR is capable of modulating Trk receptor binding properties...
  15. ncbi Differential endocytic sorting of p75NTR and TrkA in response to NGF: a role for late endosomes in TrkA trafficking
    Smita Saxena
    Division of Neuropathology, Institute of Pathology, University of Bern, CH 3010 Bern, Switzerland
    Mol Cell Neurosci 28:571-87. 2005
    ..Disrupting p75NTR recycling diminished TrkA activation in response to low concentrations of NGF, demonstrating a functional role for the recycling of p75NTR...
  16. pmc Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair
    A Micera
    Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
    Proc Natl Acad Sci U S A 98:6162-7. 2001
    ..These data show a direct pro-fibrogenic effect of NGF on skin and lung fibroblasts and therefore indicate a role for NGF in tissue repair and fibrosis...
  17. ncbi ProNGF inhibits NGF-mediated TrkA activation in PC12 cells
    Bettina Sobottka
    F Hoffmann La Roche Ltd, CNS Preclinical Research, Grenzacherstrasse 124, 4070 Basel, Switzerland
    J Neurochem 107:1294-303. 2008
    ..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...
  18. ncbi Ligand-induced internalization of the p75 neurotrophin receptor: a slow route to the signaling endosome
    Francisca C Bronfman
    Molecular Neurobiology Group, Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Neurosci 23:3209-20. 2003
    ..These data suggest that signaling endosomes containing activated p75 are involved in neurotrophin signaling, and that such endosomes may be temporally and spatially distinct from those containing trk receptors...
  19. pmc Molecular kinetics of nerve growth factor receptor trafficking and activation
    Jerome Jullien
    Differentiation and Cell Cycle Group, Laboratoire de Biologie Moleculaire et Cellulaire, CNRS UMR 5665, Ecole Normale Superieure de Lyon, 46 allee d Italie, 69364 Lyon Cedex 07, France
    J Biol Chem 277:38700-8. 2002
    ..Together, these data show that the primary effect of NGF treatment is a p75(NTR)-modulated decrease in TrkA transit time at the cell surface...
  20. ncbi The Chagas' disease parasite Trypanosoma cruzi exploits nerve growth factor receptor TrkA to infect mammalian hosts
    Milena de Melo-Jorge
    Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA
    Cell Host Microbe 1:251-61. 2007
    ..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...
  21. ncbi Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA): mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor
    Y Indo
    Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto, Japan
    Hum Mutat 18:462-71. 2001
    ..Defects in NGF signal transduction at the TRKA receptor lead to failure to support survival of sympathetic ganglion neurons and nociceptive sensory neurons derived ..
  22. pmc Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo
    I Farinas
    Department of Physiology, University of California, San Francisco 94143, USA
    Neuron 21:325-34. 1998
    ..Results also indicate that survival of cells expressing both receptors can be maintained by activation of either one alone. NT-3 can thus activate more than one Trk receptor in vivo, which when coexpressed are functionally redundant...
  23. pmc Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor
    A Chittka
    Cell Biology Program, Weill Graduate School of Cornell University Medical College, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 96:10705-10. 1999
    ..The translocation of SC-1 to the nucleus was specific for p75, as NGF binding to the TrkA receptor did not lead to nuclear localization of SC-1...
  24. pmc The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3
    C Cordon-Cardo
    Department of Molecular Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
    Cell 66:173-83. 1991
    ..These results indicate that the product of the trk proto-oncogene is sufficient to mediate signal transduction processes induced by NGF and NT-3, at least in proliferating cells...
  25. ncbi 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
    Soledad Urra
    Department of Physiology, Center for Cellular Regulation and Pathology Joaquin V Luco, Faculty of Biological Sciences, Pontificia Universidad Catolica, Alameda 340, Santiago 8320000, Chile
    J Biol Chem 282:7606-15. 2007
    ..We demonstrate that activation of the TrkA receptor upon binding of nerve growth factor (NGF) regulates the metalloprotease-mediated shedding of p75 leaving a ..
  26. ncbi Expression of Trk tyrosine kinase receptor is a biologic marker for cell proliferation and perineural invasion of human pancreatic ductal adenocarcinoma
    Y Sakamoto
    Department of Surgery, Saga Medical School, Saga 849 8501, Japan
    Oncol Rep 8:477-84. 2001
    ..The present findings revealed a novel mechanism in PDAC progression that is mediated via a NTs-Trk interaction...
  27. ncbi Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain
    Chih Li Chen
    Dana Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA
    Neuron 49:365-77. 2006
    ..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...
  28. pmc Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules
    Takeshi Nakamura
    Department of Molecular Genetics, National Institute for Longevity Sciences, Program of Protecting the Brain, CREST, JST, Oobu, Aichi 474 8522, Japan
    Mol Cell Biol 22:8721-34. 2002
    ..These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases...
  29. ncbi A TrkA-selective, fast internalizing nerve growth factor-antibody complex induces trophic but not neuritogenic signals
    H U Saragovi
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 273:34933-40. 1998
    ..mAb does not. Thus, an absolute separation of trophic and neuritogenic function is seen for NGF.mAb, suggesting that biological response modifiers of neurotrophins can afford ligands with selected activities...
  30. ncbi Production of nerve growth factor by mouse hepatocellular carcinoma cells and expression of TrkA in tumor-associated arteries in mice
    Kan Kishibe
    Department of Pathology, Asahikawa Medical College, Midorigaoka, Japan
    Gastroenterology 122:1978-86. 2002
    ..We found that NGF is specifically elevated in mouse hepatocellular carcinomas (HCCs) by cDNA array analysis. The present study aimed to elucidate expression of NGF and its receptors during hepatocarcinogenesis and under other conditions...
  31. pmc Proneurotrophins require endocytosis and intracellular proteolysis to induce TrkA activation
    Jacqueline Boutilier
    Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal H3A 2B4, Canada
    J Biol Chem 283:12709-16. 2008
    ..However, endocytosis and cleavage of proneurotrophins produce processed forms of neurotrophins that are capable of inducing Trk activation...
  32. pmc TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells
    Ursula Funfschilling
    Program in Neuroscience, Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143 0723, USA
    J Comp Neurol 480:392-414. 2004
    ..Many types of nonneuronal cells affiliated with hair follicles and blood vessels also express TrkC-reporter but lack immunodetectable TrkC...
  33. ncbi Autophagic cell death induced by TrkA receptor activation in human glioblastoma cells
    Katharina Hansen
    Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Martinistrasse, Hamburg, Germany
    J Neurochem 103:259-75. 2007
    ..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...
  34. ncbi Trk receptor tyrosine kinases: a bridge between cancer and neural development
    A Nakagawara
    Division of Biochemistry, Chiba Cancer Center Research Institute, 666 2 Nitona, Chuoh ku, 260 8717, Chiba, Japan
    Cancer Lett 169:107-14. 2001
    ..In this short review, the dynamic role of the Trk family receptors signaling in neural development, neurogenic tumors and other cancers will be discussed...
  35. ncbi A synthetic peptide modeled on PDNF, Chagas' disease parasite neurotrophic factor, promotes survival and differentiation of neuronal cells through TrkA receptor
    Marina V Chuenkova
    Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, Massachusetts 02111, USA
    Biochemistry 44:15685-94. 2005
    ....
  36. ncbi Nerve growth factor enhances cough and airway obstruction via TrkA receptor- and TRPV1-dependent mechanisms
    A Z El-Hashim
    Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait
    Thorax 64:791-7. 2009
    ..Nerve growth factor (NGF) is an important mediator of airway hyper-responsiveness and hyperalgesia but its role in cough is unknown...
  37. ncbi Neutralization of NGF-TrkA receptor interaction by the novel antagonistic anti-TrkA monoclonal antibody MNAC13: a structural insight
    Sonia Covaceuszach
    LaylineGenomics, Roma, Italy
    Proteins 58:717-27. 2005
    ..The structure of the MNAC13 Fab fragment may assist in the rational structure-based design of high affinity humanized forms of MNAC13, appropriate for therapeutic approaches in neuropathy and inflammatory pain states...
  38. ncbi Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils
    O Noga
    Allergy and Asthma Clinic, Charite, Campus Virchow, Humboldt University, Berlin, Germany
    Clin Exp Allergy 32:1348-54. 2002
    ..Recent studies have shown that nerve growth factor (NGF) can act on several immune cells as well as residential cells. But little is known about their role in modulating eosinophil function via activation of high-affinity receptors...
  39. ncbi Expression and activation of the nerve growth factor receptor TrkA in serous ovarian carcinoma
    Ben Davidson
    Department of Pathology, The Norwegian Radium Hospital, Montebello N 0310 Oslo, Norway
    Clin Cancer Res 9:2248-59. 2003
    ..In addition, we wished to study the possible link between expression of NGF, a novel angiogenic factor and its receptor TrkA, and the expression of factors involved in angiogenesis in effusions and solid tumors...
  40. ncbi Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice
    C E Van der Zee
    Department of Anatomy and Neurobiology, Tupper Building, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada
    Science 274:1729-32. 1996
    ..Apparently, p75(NGFR) mediates apoptosis of these developing neurons in the absence of TrkA, and modulation of p75(NGFR) can promote neuronal survival. Cholinergic basal forebrain neurons are involved in learning and memory...
  41. pmc Immunohistochemical evaluation of the protein expression of nerve growth factor and its TrkA receptor in rat limbic regions following electroshock seizures
    Giuseppe Conti
    Department of Pharmacology, Georgetown University, Washington, DC 20057, USA
    Neurosci Res 65:201-9. 2009
    ..The neuroprotective action of NGF is mediated by the TrkA receptor. This study determined whether repeated ECS exposure increased TrkA and NGF protein levels...
  42. ncbi The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation
    S O Meakin
    Neurodegeneration Research Group, The John P Robarts Research Institute, London, Ontario N6A 5K8, Canada
    J Biol Chem 274:9861-70. 1999
    ..Importantly, overexpression of FRS-2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes the ability of NGF to stop cell cycle progression and to stimulate neuronal ..
  43. ncbi Nerve growth factor activates persistent Rap1 signaling in endosomes
    C Wu
    Departments of Neurology and Neurological Sciences and of Pediatrics and the Program in Neuroscience, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurosci 21:5406-16. 2001
    ..We propose that endosomes are a site from which NGF induces the prolonged activation of Rap1 and MAPK...
  44. ncbi Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation
    Y Zhang
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 20:5671-8. 2000
    ..Thus, interactions between Trk receptor tyrosine kinases and intracellular signaling molecules are dictated both by phosphotyrosine motifs within the receptors and by the intracellular location of phosphorylated receptors...
  45. ncbi NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination
    Xinhua Lee
    Department of Discovery Biology, Biogen Idec, Cambridge, Massachusetts 02142, USA
    J Neurosci 27:220-5. 2007
    ..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...
  46. ncbi Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation
    Juan Carlos Arevalo
    Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, NY 10016, USA
    J Biol Chem 281:1001-7. 2006
    ..Therefore, Trk receptor signaling involves an inducible switch mechanism through an unconventional substrate that distinguishes neurotrophin action from other growth factor receptors...
  47. ncbi The nerve growth factor precursor proNGF exhibits neurotrophic activity but is less active than mature nerve growth factor
    Margaret Fahnestock
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
    J Neurochem 89:581-92. 2004
    ..These data, coupled with our previous report that proNGF is the major form of NGF in the CNS, suggest that proNGF could be responsible for much of the biological activity normally attributed to mature NGF in vivo...
  48. ncbi Nerve growth factor expression and innervation of the painful intervertebral disc
    A J Freemont
    Manchester University, UK
    J Pathol 197:286-92. 2002
    ..These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies...
  49. pmc Trk-signaling endosomes are generated by Rac-dependent macroendocytosis
    Gregorio Valdez
    Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794 5230, USA
    Proc Natl Acad Sci U S A 104:12270-5. 2007
    ..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...
  50. ncbi Autophosphorylation of activation loop tyrosines regulates signaling by the TRK nerve growth factor receptor
    M E Cunningham
    Department of Pathology and Center of Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 272:10957-67. 1997
    ....
  51. pmc Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death
    Sung Wuk Jang
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 104:16329-34. 2007
    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...
  52. ncbi Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclase-activating polypeptides
    Francis S Lee
    Department of Psychiatry, Weill Medical College, Cornell University, New York, New York 10021, USA
    J Biol Chem 277:9096-102. 2002
    ..This ability may explain several neuroprotective actions of PACAP upon neuronal populations after injury, nerve lesion, or neurotrophin deprivation...
  53. pmc The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons
    Frederic Marmigere
    Laboratory of Molecular Neurobiology, Karolinska Institute, MBB, Scheeles vag 1, Stockholm, Sweden
    Nat Neurosci 9:180-7. 2006
    ..Our data show that Runx1 directs, in a context-dependent manner, key aspects of the establishment of the TrkA(+) nociceptive subclass of neurons...
  54. ncbi Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma
    O Gimm
    Comprehensive Cancer Center, Ohio State University, Columbus 43210, USA
    J Clin Endocrinol Metab 84:2784-7. 1999
    ....
  55. ncbi On Trk for retrograde signaling
    F D Miller
    Center for Neuronal Survival and Brain Tumor Research Center, Montreal Neurological Institute, McGill University, 3801 rue University, H3A 2B4, Montreal, Quebec, Canada
    Neuron 32:767-70. 2001
    ....
  56. ncbi Constitutively active Src facilitates NGF-induced phosphorylation of TrkA and causes enhancement of the MAPK signaling in SK-N-MC cells
    Akinori Tsuruda
    Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305 8572, Japan
    FEBS Lett 560:215-20. 2004
    ..These results suggest that constitutively active Src that associates with TrkA through Grb2 after NGF stimulation participates in TrkA phosphorylation and in turn enhances the mitogen-activated protein kinase signaling in SK-N-MC cells...
  57. ncbi Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons
    Long Ma
    Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390 9133, USA
    Development 130:3525-34. 2003
    ..Thus, TrkA, a gene that is crucial for the differentiation and survival of sensory nociceptive neurons, requires Brn3a to maintain normal transcriptional activity...
  58. ncbi Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex
    A Obermeier
    Department of Molecular Biology, Max Planck Institut fur Biochemie, Martinsried, Germany
    J Biol Chem 268:22963-6. 1993
    ..In spite of the close proximity of the p85 binding site to that of phospholipase C gamma (Y-785), both target proteins are able to interact with the same receptor molecule simultaneously...
  59. ncbi Tissue-specific alternative splicing generates two isoforms of the trkA receptor
    P A Barker
    Department of Neurobiology, Stanford University, California 94305 5401
    J Biol Chem 268:15150-7. 1993
    The trkA receptor functions as a signal transducing receptor for nerve growth factor. In this report, we show that alternative splicing results in the production of two distinct trkA isoforms in both rats and humans...
  60. ncbi Brn3a and Klf7 cooperate to control TrkA expression in sensory neurons
    Lei Lei
    Center for Developmental Biology and Kent Waldrep Center for Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390 9133, USA
    Dev Biol 300:758-69. 2006
    ..Thus, cooperation between these two transcription factors is required for endogenous TrkA gene expression and the survival of nociceptive sensory neurons...
  61. ncbi Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells
    Z W Zhu
    Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland
    Clin Cancer Res 7:105-12. 2001
    ..These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy...
  62. ncbi An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors
    H Kong
    Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    J Neurosci 21:176-85. 2001
    ....
  63. ncbi NGF activates the phosphorylation of MAP1B by GSK3beta through the TrkA receptor and not the p75(NTR) receptor
    Robert G Goold
    The MRC Centre for Developmental Neurobiology, King s College London, London, UK
    J Neurochem 87:935-46. 2003
    ..Finally, inhibition of TrkA receptor tyrosine kinase activity in PC12 cells and superior cervical ganglion neurons with K252a potently and dose-..
  64. pmc Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1
    H Keilhack
    Research Unit, Molecular Cell Biology, D 07747 Jena, Germany
    J Cell Biol 152:325-34. 2001
    ..Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling...
  65. ncbi Changes in retinal expression of neurotrophins and neurotrophin receptors induced by ocular hypertension
    Marcelo Rudzinski
    Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
    J Neurobiol 58:341-54. 2004
    ..A possible rationale for therapeutic intervention with Trk receptor agonists and p75 receptor antagonists is proposed...
  66. pmc NGF controls axonal receptivity to myelination by Schwann cells or oligodendrocytes
    Jonah R Chan
    Department of Neurobiology, Stanford University School of Medicine, Fairchild Science Building D235, CA 94305, USA
    Neuron 43:183-91. 2004
    ..These findings indicate a novel role for growth factors in regulating the receptivity of axons to myelination and reveal that different axonal signals control central and peripheral myelination...
  67. ncbi Nerve growth factor activation of the TrkA receptor induces cell death, by macropinocytosis, in medulloblastoma Daoy cells
    Chunhui Li
    Laboratory of Neural Signalling, The Robarts Research Institute, London, Ontario, Canada
    J Neurochem 112:882-99. 2010
    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...
  68. ncbi Absence of p75NTR causes increased basal forebrain cholinergic neuron size, choline acetyltransferase activity, and target innervation
    T T Yeo
    Department of Neurology, University of California at San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, USA
    J Neurosci 17:7594-605. 1997
    ..These findings indicate that p75NTR negatively regulates cholinergic neuronal phenotype of the basal forebrain cholinergic neurons, including cell size, target innervation, and neurotransmitter synthesis...
  69. ncbi Identification and characterization of novel substrates of Trk receptors in developing neurons
    X Qian
    Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Neuron 21:1017-29. 1998
    ..Together, these observations indicate that rAPS and SH2-B mediate Trk signaling in developing neurons...
  70. ncbi Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord
    Michael K Gross
    Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuron 34:535-49. 2002
    ..Lbx1, therefore, plays a critical role in the development of sensory pathways in the spinal cord that relay pain and touch...
  71. ncbi Remodeling of the innervation of pancreatic islets accompanies insulitis preceding onset of diabetes in the NOD mouse
    Solveig Persson-Sjögren
    Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umea University, SE 901 87 Umea, Sweden
    J Neuroimmunol 158:128-37. 2005
    ....
  72. ncbi Distinct effects of p75 in mediating actions of neurotrophins on basal forebrain oligodendrocytes
    Yangzhou Du
    Department of Neuroscience and Cell Biology, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Mol Cell Neurosci 31:366-75. 2006
    ..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...
  73. pmc Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity
    N Y Ip
    Regeneron Pharmaceuticals, Inc, Tarrytown, NY 10591
    Proc Natl Acad Sci U S A 89:3060-4. 1992
    ..However, mammalian NT-4 displays bioactivity and trk receptor specificity similar to that of Xenopus NT-4...
  74. ncbi Expression of NGF, Trka and p75 in human cartilage
    A Gigante
    Clinica Ortopedica, Universita di Ancona, Via Tronto 10, 60020 Torrette di Ancona, Italy
    Eur J Histochem 47:339-44. 2003
    ....
  75. pmc 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
    Marcela Julio-Pieper
    Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clinico Universidad de Chile, Santos Dumont 999 Independencia, Santiago, Chile
    J Clin Endocrinol Metab 94:3065-71. 2009
    ..Nerve growth factor (NGF) may be one of these factors, because NGF promotes angiogenesis and synthesis of angiogenic factors in other tissues and is produced by human granulosa cells (hGCs)...
  76. ncbi Neural crest development and neuroblastoma: the genetic and biological link
    Akira Nakagawara
    Division of Biochemistry, Chiba Cancer Center Research Institute, 666 2 Nitona, Chuoh ku, Chiba 260 8717, Japan
    Prog Brain Res 146:233-42. 2004
    ..Thus, the enigmatic clinical behaviors of neuroblastoma are strictly linked to the molecular mechanism of neural crest development...
  77. ncbi The p75 neurotrophin receptor: multiple interactors and numerous functions
    Jannifer J Gentry
    Center for Molecular Neuroscience, Department of Biochemistry, Vanderbilt University Medical School, Nashville, TN 37232, USA
    Prog Brain Res 146:25-39. 2004
    ..Here, we review these p75NTR interacting factors and the current evidence as to how they contribute to the functional effects of p75NTR activation...
  78. ncbi Tyr-701 is a new regulatory site for neurotrophin receptor TrkA trafficking and function
    Yolanda de Pablo
    Cell Signaling and Apoptosis Group, Department Ciències Médiques Bàsiques, IRBLLEIDA, Lleida, Spain
    J Neurochem 104:124-39. 2008
    ..This is the first evidence that a Tyr residue can simultaneously regulate TrkA receptor trafficking and activity.
  79. ncbi Activation of the ERK1/2 and p38 mitogen-activated protein kinase pathways mediates fibroblast growth factor-induced growth arrest of chondrocytes
    Angela Raucci
    Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    J Biol Chem 279:1747-56. 2004
    ..These results indicate that inhibition of chondrocyte proliferation by FGF requires both ERK1/2 and p38 MAPK signaling and also suggest that sustained activation of these pathways is required to achieve growth inhibition...
  80. ncbi Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor
    Kwang Mook Jung
    Department of Pathology, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Biol Chem 278:42161-9. 2003
    ..our studies suggest that gamma-secretase-mediated p75NTR proteolysis plays a role in the formation/disassembly of the p75-TrkA receptor complex by regulating the availability of the p75 TM domain that is required for this interaction.
  81. ncbi Recent advances in hereditary sensory and autonomic neuropathies
    Kristien Verhoeven
    Peripheral Neuropathy Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Curr Opin Neurol 19:474-80. 2006
    ..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...
  82. ncbi Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells
    Sujata Sundara Rajan
    Department of Biomedical Engineering, Oregon Health and Science University, Beaverton, Oregon 97006 8921, USA
    Nano Lett 6:2049-59. 2006
    ..QDs are contained in microtubule-associated vesicles and possess transport properties that reflect TrkA receptor dynamics...
  83. ncbi Molecular genetics of hereditary sensory neuropathies
    Michaela Auer-Grumbach
    Department of Internal Medicine, Medical Research Center, Medical University of Graz, Stiftingtalstrasse 24, A 8010 Graz, Austria
    Neuromolecular Med 8:147-58. 2006
    ..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...
  84. ncbi Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons
    Masaaki Yoshikawa
    Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1 1 1 Tennodai, Tsukuba 305 8577, Japan
    Dev Biol 303:663-74. 2007
    ..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...
  85. ncbi The small GTPase Rab7 controls the endosomal trafficking and neuritogenic signaling of the nerve growth factor receptor TrkA
    Smita Saxena
    Abteilung Neuropathologie, Institut fur Pathologie, Universitat Bern, CH 3010 Bern, Switzerland
    J Neurosci 25:10930-40. 2005
    Nerve growth factor (NGF) and its TrkA receptor exert important bioactivities on neuronal cells such as promoting survival and neurite outgrowth...
  86. ncbi Nerve growth factor helps protect retina in experimental retinal detachment
    Xiaodong Sun
    Eye Research Institute of Shanghai JiaoTong University, Shanghai, China
    Ophthalmologica 222:58-61. 2008
    ..To investigate the expression of nerve growth factor (NGF) and its receptor TrkA on the retina at different time points after retinal detachment (RD) and the protection effect of NGF in experimental RD...
  87. pmc Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment
    M Rihl
    Hannover Medical School MHH, Department of Rheumatology OE 6850, Carl Neuberg Str 1, 30625 Hannover, Germany
    Ann Rheum Dis 64:1542-9. 2005
    ..To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA)...
  88. ncbi Oncogenic rearrangements of the NTRK1/NGF receptor
    Marco A Pierotti
    Department of Experimental Oncology and Labs Operative Unit 3, Istituto Nazionale Tumori, Via G Venezian, 1 20133 Milan, Italy
    Cancer Lett 232:90-8. 2006
    ..The modalities of their activation, their mechanism of action, the contribution of activating sequences, and the molecular mechanisms underlying their generation will be discussed...
  89. ncbi Retinal p75 and bax overexpression is associated with retinal ganglion cells apoptosis in a rat model of glaucoma
    Marco Coassin
    CIR, Laboratory of Ophthalmology, University Campus Bio Medico, Via Alvaro del Portillo, 21, 00128, Rome, Italy
    Graefes Arch Clin Exp Ophthalmol 246:1743-9. 2008
    ..Therefore, this study sought to address whether timely changes in NGF and its receptors, trkA(NGFR) and p75(NTR), might explain the progression of retinal damage during experimental glaucoma...
  90. ncbi Humoral immunodeficiency in congenital insensitivity to pain with anhidrosis
    Sara Sebnem Kilic
    Department of Pediatric Immunology, Uludag University School of Medicine, Gorukle, Bursa, 16059, Turkey
    Neurogenetics 10:161-5. 2009
    ..The implication of the immune system of the reported patient broadens the clinical phenotype associated with NTRK1 mutations...
  91. ncbi Effect of exogenous administration of nerve growth factor in the retina of rats with inherited retinitis pigmentosa
    Laura Lenzi
    Institute of Neurobiology and Molecular Medicine, Neurobiology Section, CNR, Viale Marx 43 15, 00137 Rome, Italy
    Vision Res 45:1491-500. 2005
    ..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...
  92. ncbi Origin and evolution of the Trk family of neurotrophic receptors
    Elia Benito-Gutiérrez
    Departament de Genetica, Facultat de Biologia, Universitat de Barcelona, Avinguda Diagonal 645, Barcelona E 08028, Spain
    Mol Cell Neurosci 31:179-92. 2006
    ..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...
  93. ncbi Neurotrophic activities of trk receptors conserved over 600 million years of evolution
    Gad Beck
    Department of Biological Chemistry, Molecular Neurobiology Group, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Neurobiol 60:12-20. 2004
    ..Thus, Ltrk is required for neuronal survival, suggesting that trophic activities of the trk receptor family originated before the divergence of molluscan and vertebrate lineages approximately 600 million years ago...
  94. ncbi Neurotrophic factor expression in childhood low-grade astrocytomas and ependymomas
    Antonio Chiaretti
    Paediatric Intensive Care Unit, Catholic University of Sacred Heart, 00168 Rome, Italy
    Childs Nerv Syst 20:412-9. 2004
    ..In accordance with the role of neurotrophic factors in tumour behaviour the aim of the present study was to investigate their expression in two childhood brain neoplasms, namely low-grade astrocytomas and ependymomas...
  95. ncbi TrkA receptor "hot spots" for binding of NT-3 as a heterologous ligand
    Ljubica Ivanisevic
    Lady Davis Institute Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada
    J Biol Chem 282:16754-63. 2007
    ..This study demonstrates that Trk signaling is more complex than previously thought because it involves several receptor subdomains and hot spots...
  96. ncbi Decreased first phase insulin response in children with congenital insensitivity to pain with anhidrosis
    Ruth Schreiber
    Pediatric Department, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
    J Pediatr Endocrinol Metab 18:873-7. 2005
    ..Additional studies on the clinical significance of NGF-TrkA effects on insulin secretion are required...
  97. ncbi Proinflammatory cytokines stimulate the expression of nerve growth factor by human intervertebral disc cells
    Yumiko Abe
    Department of Orthopedic Surgery, Rush Medical College at Rush University Medical Center, Chicago IL, USA
    Spine (Phila Pa 1976) 32:635-42. 2007
    ..In vitro studies of the effects of proinflammatory cytokines on the production of nerve growth factor (NGF) by human intervertebral disc (IVD) cells...
  98. ncbi Neurotrophin signalling in health and disease
    Moses V Chao
    Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA
    Clin Sci (Lond) 110:167-73. 2006
    ..In this review, we consider the signalling pathways activated by neurotrophins in both health and disease states...
  99. ncbi High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor
    B L Hempstead
    Department of Medicine, Cornell University Medical College, New York, New York 10021
    Nature 350:678-83. 1991
    ..These studies reveal a new growth factor receptor-mediated mechanism of cellular differentiation involving trk and the low-affinity NGF receptor...
  100. ncbi Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies
    S Shatzky
    Genetics Institute, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel
    Am J Med Genet 92:353-60. 2000
    ..Three polymorphisms in the TrkA protein kinase encoding domain were also observed...
  101. pmc Trafficking of TrkA-green fluorescent protein chimerae during nerve growth factor-induced differentiation
    Jerome Jullien
    Differentiation and Cell Cycle Group, Laboratoire de Biologie Moleculaire et Cellulaire, UMR 5665 CNRS, Ecole Normale Superieure de Lyon, France
    J Biol Chem 278:8706-16. 2003
    ..This approach and the fidelity of the biochemical properties of the TrkA-GFP demonstrate that real-time visualization of trafficking of tyrosine kinase receptors in the presence or absence of the ligand is feasible...

Research Grants62

  1. Imaging NGF signal transduction in live neurons
    Bianxiao Cui; Fiscal Year: 2010
    ..NGF-lacking endosomes with photo-activatable green fluorescence proteins that are fused to the C-terminal of TrkA receptor. 3...
  2. Neurotrophin mechanisms in neural development and disease
    Rejji Kuruvilla; Fiscal Year: 2013
    ..that two different neurotrophins, Nerve Growth Factor (NGF) and Neurotrophin-3 (NT-3), employ the same TrkA receptor to promote sequential stages of axonal growth during sympathetic nervous system development...
  3. Remark bundle structure and function in neuropathic pain
    John W Griffin; Fiscal Year: 2010
    ..changes, new models of selective nociceptor injury, and a new genetically engineered mouse in which a TrkA receptor kinase mutation is "knocked-in" so that the TrkA is blocked in its signaling by a small molecule inhibitor, ..
  4. BLADDER HYPERACTIVITY AFTER OBSTRUCTION RELIEF
    William Steers; Fiscal Year: 1999
    ..voiding frequency, and 3) noting if tyrosine kinase inhibitors that block the effects of NGF binding to the trkA receptor prevent myogenic or neural plasticity and urinary frequency...
  5. Cholinergic and cognitive decline in response to TrkA knockdown using RNAi
    Vinay Parikh; Fiscal Year: 2009
    ..under the control of a RNA polymerase II promoter, and screening of TrkA miRNA sequences for suppression of TrkA receptor expression in rat pheochromocytoma cells...
  6. Specific targeting of a neuronal subset using a novel chimeric vector pseudotype
    CHRISTOPHER TRIMBY; Fiscal Year: 2009
    ..Loop 2 confers the ability of NGF to bind the TrkA receptor, which is a receptor that is primarily expressed on sensory neurons including those projecting from the dorsal ..
  7. NGF SIGNALING IN MODELS OF AGE RELATED NEURODEGENERATION
    William Mobley; Fiscal Year: 2002
    ..in which one copy of the NGF gene has been disrupted, and mice in which both copies of the gene for the NGF TrkA receptor has been knocked-out. 4) To define NGF actions on degenerating BFCNs in Ts65Dn...
  8. STRUCTURE/FUNCTION OF TRK RECEPTORS FOR NEUROTROPHINS
    KENNETH NEET; Fiscal Year: 2001
    ..The hypothesis being tested is that multiple subdomains of the extracellular domain of the TrkA receptor simultaneously interact with numerous distinct regions of NGF...
  9. IDENTIFICATION OF A NOVEL SIGNAL PATHWAY FOR NGF
    Raymond Birge; Fiscal Year: 2003
    ..In the present application, we shall study the molecular mechanisms by which c-Crk couples the TrkA receptor to the cytoskeleton, with the long-term goal to understand how NGF promotes differentiation and survival...
  10. NEURAL STEM CELLS AND NEURO-ONCOLOGY
    Lawrence Recht; Fiscal Year: 2002
    ..Project 4 focuses on the ability of Trka receptor transduction to alter the biologic behavior of C6 glioma cells...
  11. TRK RECEPTORS AND NEUROTROPHINS
    Luis Parada; Fiscal Year: 2005
    ..the third aim, we will exploit the existence of a TrkA enhancer, to perform structure/function analysis of the TrkA receptor in vivo...
  12. Combinatorial Approaches to Activators of the NGF Recep*
    Nicholas Webster; Fiscal Year: 2005
    ..closely related structures would be a valuable resource for the discovery of small molecule activators of the TrkA receptor. In this proposal, we would like to explore this hypothesis by screening this combinatorial library against ..
  13. TOOLS FOR THE DISSECTION OF PAIN TRANSMISSION PATHWAYS
    DOUGLAS LAPPI; Fiscal Year: 1999
    ..COMMERCIAL APPLICATIONS: This proposal seeks to develop an immunolesioning tool for neurons that express the TrkA receptor, the signal transduction receptor for NGF...
  14. Antipsychotics: Temporal Effects on Cognitive Function
    Alvin Terry; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  15. Cotinine for Cognitive Impairment in Neurological and Neuropsychiatric Disorders
    Alvin V Terry; Fiscal Year: 2010
    ..The partly translational design of the study will provide results leading to eventual clinical trials with cotinine or a relevant analog. ..
  16. Trk receptor mediated apoptosis of medulloblastoma cells
    Paul Mischel; Fiscal Year: 2005
    ..This team of internationally recognized mentors is committed to helping Dr. Mischel meet all of the aims of this proposal, and to ensure that he develops into an outstanding independent investigator. ..
  17. Katzir Conference on Life and Death in the Nervous System
    Moses Chao; Fiscal Year: 2008
    ..The meetings have been a very effective means of stimulating new research and attracting new scientists to the field. [unreadable] [unreadable] [unreadable]..
  18. Glioblastoma - Molecular Analysis for Clinical Trials
    Paul Mischel; Fiscal Year: 2009
    ..abstract_text> ..
  19. TRAINING IN AGE-RELATED NEURODEGENERATIVE DISEASES
    Elliott Mufson; Fiscal Year: 2008
    ..Finally the program will provide a broad-base of knowledge on neurodegenerative disorders as well as other instruction important for enhancing the interpersonal and professional skills of our trainees. ..
  20. Validating microRNA Analysis in Human Postmortem Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  21. Neurotrophic factors and excitability
    Grant Nicol; Fiscal Year: 2007
    ..A fundamental understanding of such events could lead to better designed compounds and therapies to facilitate the treatment of chronic inflammatory conditions. [unreadable] [unreadable]..
  22. Molecular Targeting and Imaging of Pituitary Adenomas
    NELSON OYESIKU; Fiscal Year: 2008
    ..These experiments capitalize on our findings of selective overexpression of functional FRa in NF adenomas, thereby translating basic research into clinical application. ..
  23. BAC-FISH Assays for Sensitive Karyotyping of Cancer Cells
    Heinz Ulrich Weier; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  24. Regulation of Neurotrophin Receptor Trafficking
    Francis Lee; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  25. INTERVENTIONS TO PREVENT NOISE INDUCED HEARING LOSS
    JOSEF MILLER; Fiscal Year: 2007
    ..We will also determine if reduced blood flow potentiates NIHL, in vivo. These studies will define new interventions and synergies at sites along the apoptotic pathway to optimize the prevention of NIHL. ..
  26. AGRIN GENE EXPRESSION
    Martin Smith; Fiscal Year: 2009
    ..The results of these studies, therefore, are likely to be directly relevant to the prevention and treatment of a number of human disorders, such as epilepsy, that disrupt behavior of neural circuits. ..
  27. Sphingosine 1-Phosphate Receptors and Sensitization of Sensory Neurons
    Grant D Nicol; Fiscal Year: 2010
    ..abstract_text> ..
  28. Pro- and Anti-Nociceptive Actions of P2y Nucleotide Receptors in Sensory Neurons
    Derek C Molliver; Fiscal Year: 2010
    ....
  29. Divergence and maturation of autonomic lineages
    SUSAN BIRREN; Fiscal Year: 2009
    ....
  30. TISSUE ENGINEERING IN THE INNER EAR
    JOSEF MILLER; Fiscal Year: 2005
    ....
  31. Vascular Mechanosensor
    Heather A Drummond; Fiscal Year: 2010
    ..Results from this proposal will help define the molecular mechanism of myogenic constriction and provide a better understanding of pressure induced end organ damage. ..
  32. Cholinergic Lesions and Age-Related Cognitive Impairment
    Robert Gibbs; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  33. Muller glia and neuronal regeneration in the retina
    Andy Fischer; Fiscal Year: 2009
    ..This information could be applied to not only stimulate neural regeneration to treat sight-threatening diseases of the retina, but also to control gliosis that may be detrimental to the pathogenesis of retinal disorders. ..
  34. NEUROENDOCRINOLOGY OF PUBERTY AND SEXUAL DEVELOPMENT
    Sergio R Ojeda; Fiscal Year: 2010
    ..4) To examine the hypothesis that a novel gene, termed EAP-1 (Enhanced At. Puberty-1) belongs - along with TTF-1 - to the hierarchy of controlling genes involved in the transcriptional regulation of the pubertal process. ..
  35. WORKSHOP/USE OF NONHUMAN PRIMATES/NEUROSCIENCE RESEARCH
    Sergio Ojeda; Fiscal Year: 2002
    ....
  36. Ethanol, neurotrophins, and thalamocortical matching
    SANDRA MOONEY; Fiscal Year: 2006
    ..abstract_text> ..
  37. A Novel Gene Network Controlling Mammalian Puberty
    Sergio Ojeda; Fiscal Year: 2006
    ..Although siRNAs are widely used to perturb gene expression in mammalian cells, the methodology to achieve long-term silencing effects in vivo is still in its infancy. [unreadable] [unreadable]..
  38. NEUROTROPHIN CONTROL OF REM SLEEP
    Jack Yamuy; Fiscal Year: 2004
    ..This concerted set of experiments will be critical in elucidating the role that neurotrophins play in the control of REM sleep. ..
  39. Regulated Ligand Access in Control Receptor Processes
    H Wiley; Fiscal Year: 2004
    ..In addition, they should provide some general insights into how other growth factor systems are regulated. ..
  40. Neuronal mRNA transport & local translation analysis
    Jeffery Twiss; Fiscal Year: 2004
    ..g., spinal motor neurons) and whether we can utilize exogenous agents to increase local axonal protein synthesis for expediting axonal regeneration. ..
  41. DEVELOPMENT AND MODULATION OF AUTONOMIC SYNAPSES
    SUSAN BIRREN; Fiscal Year: 2004
    ..These experiments will, for the first time, define the developmental and modulatory roles of NGF at the synaptic level. ..
  42. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2003
    ..This will determine how anti-Abeta antibodies influence CNS/plasma Abeta transport exchanges. ..
  43. IL-6 IN HERPES SIMPLEX VIRUS TYPE 1 OCULAR REACTIVATION
    JOHN KRIESEL; Fiscal Year: 2002
    ..Novel and specific viral mutants will be constructed based on the results of HSV-DNA binding and transient expression assays. ..
  44. INACTIVATION OF SENSITIZATION IN SENSORY NEURONS
    Grant Nicol; Fiscal Year: 2003
    ..abstract_text> ..
  45. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2003
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..
  46. Molecular Diagnosis Utilizing Cerebrospinal Fluid
    STEPHEN GINSBERG; Fiscal Year: 2003
    ..abstract_text> ..
  47. Lesion Induced Synaptic Plasticity
    STEPHEN GINSBERG; Fiscal Year: 2004
    ....
  48. POSTRECEPTOR DYSREGULATION IN DEPRESSION
    Yogesh Dwivedi; Fiscal Year: 2004
    ..abstract_text> ..
  49. Neuronal subsets in the geniculate ganglion
    Albert Farbman; Fiscal Year: 2005
    ..We shall use in vitro and in vivo methods to relate changes in trk expression during development to other major developmental events. ..
  50. A Novel Genetic Therapy for Herpes Keratitis
    JOHN KRIESEL; Fiscal Year: 2006
    ..An ex vivo model of HSV-1 reactivation in explanted mouse trigeminal ganglia is proposed as an efficient means for determining effective strategies for the delay or inhibition of reactivation. ..
  51. Proteomics of mild cognitive impairment in the elderly
    SCOTT COUNTS; Fiscal Year: 2006
    ..Both of these factors will be critical for the development of neuroprotective strategies for slowing or preventing cognitive decline in the elderly. ..
  52. NEUROPATHOLOGY OF THE AGING SYMPATHETIC NERVOUS SYSTEM
    Robert Schmidt; Fiscal Year: 2006
    ..The results of these experiments should provide insight not only into autonomic dysfunction, but into a variety of pathologic processes in which NAD is a prominent component. ..
  53. LSM 510 Confocal Microscope
    Robert Gibbs; Fiscal Year: 2006
    ..Acquisition of the requested instrument will eliminate this problem, and will provide the School of Pharmacy with a greatly needed resource. [unreadable] [unreadable] [unreadable]..
  54. RADIATION INDUCED THYROID CANCER
    Heinz Ulrich Weier; Fiscal Year: 2002
    ..We will prepare stable cell lines carrying the oncogenic rearrangements for further characterization and distribution. Finally, we will examine the levels and localization of mRNAs with Northern and in situ hybridization analysis. ..
  55. A New Tool for Targeted Antisense Knockdown in Brain
    Robert Gibbs; Fiscal Year: 2006
    ..This will be the first time that a targeted antisense knockdown approach will have been developed and used to selectively regulate gene expression within an identified subpopulation of neurons in the adult brain. ..
  56. Molecular Specifiers of Neural Cell Plasticity
    Sergio Ojeda; Fiscal Year: 2006
    ..abstract_text> ..
  57. Neuroblastoma Biology and Therapy
    GARRETT BRODEUR; Fiscal Year: 2007
    ..Furthermore, treatment strategies developed against neuroblastoma may be useful against other tumors in children and adults that are rely on the biological pathways and are affected by these agents. ..
  58. Synaptic Alterations in the Cerebral Cortex during Aging
    A Cuello; Fiscal Year: 2005
    ..abstract_text> ..
  59. ACTIONS OF PROINFLAMMATORY CYTOKINES ON SENSORY NEURONS
    Grant Nicol; Fiscal Year: 2002
    ..The results of this work can increase the understanding of the cellular mechanisms mediating the interaction between the nervous system and the immune system and thus be applicable to other areas of neurobiology. ..
  60. Mechanism of Mechanoreceptor Inhibition by Aldosterone
    Heather Drummond; Fiscal Year: 2006
    ..unreadable] [unreadable]..