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Gene Review

NGFR  -  nerve growth factor receptor

Homo sapiens

Synonyms: CD271, Gp80-LNGFR, Low affinity neurotrophin receptor p75NTR, Low-affinity nerve growth factor receptor, NGF receptor, ...
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Disease relevance of NGFR


Psychiatry related information on NGFR


High impact information on NGFR

  • Surprisingly, the 55 kd TNF receptor shows a high degree of sequence homology to the NGF receptor extracellular domain [7].
  • Transfection of a full-length cDNA in mouse fibroblasts results in stable expression of NGF receptors that are recognized by monoclonal antibodies to the human NGF receptor and that bind [125I]NGF [8].
  • Induction of apoptosis by the low-affinity NGF receptor [9].
  • These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins [10].
  • Neurite outgrowth was not observed with chimeric receptors that contained the transmembrane domain from the EGFR, suggesting that the membrane-spanning region and cytoplasmic domain of the low-affinity NGFR are necessary for signal transduction [11].

Chemical compound and disease context of NGFR


Biological context of NGFR

  • Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages [17].
  • Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high- and low-affinity binding sites [1].
  • The transformant line LAN5/NGFR expressed both high- and low-affinity NGFRs, displayed NGF-induced up-regulation of fos oncogene, and efficiently internalized NGF [18].
  • However, high expression levels of nerve growth factor receptor (NGFR), neural cell adhesion molecule (N-CAM), and cell adhesion molecule L1 (L1) were observed [19].
  • Inhibition of NGFR tyrosine phosphorylation had no effect but the src inhibitor PP1 abolished MAPK and Akt phosphorylation in all three clones [20].

Anatomical context of NGFR


Associations of NGFR with chemical compounds

  • Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR) [3].
  • Also, the expression of different species of NGFR could be modified by treatment with retinoic acid (RA) [25].
  • NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, P<0.0001) [26].
  • A chimeric gene consisting of 6.7 kb of the 5'-flanking region of the human NGFR gene linked to the chloramphenicol acetyltransferase gene was constructed [27].
  • For 28 sets of serial examinations, NGFR was also measured by the plasma disappearance of 99mTc DTPA (measured) [28].

Physical interactions of NGFR

  • The number of high-affinity NGF binding sites was nearly the same for LAN5 and LAN5/NGFR, a finding suggesting that there is a limiting number of some separately coded factor or subunit that is required for high-affinity NGFRs [18].
  • Results obtained with cells transfected with the low-affinity NGF receptor gene indicate that these cells bind BDNF, in addition to NGF, whereas cells before transfection do not [29].
  • The high-affinity NGF receptor is thought to be a complex of two receptors , gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association had been lacking [30].

Co-localisations of NGFR


Regulatory relationships of NGFR


Other interactions of NGFR

  • We document the presence of RNA message for the low- (LNGFR) and the high-affinity NGF receptor (NTRK1) by using RT-PCR on fresh BM aspirate and on LTBMC [37].
  • The results demonstrate that, in addition to Grb2, CRK participates in signaling from the NGF receptor and that two GNRPs appear to transmit signals from these adaptor molecules to Ras [38].
  • Furthermore, colocalization studies show that many BDNF-expressing sensory neurons also express trk A, the high-affinity NGF receptor [39].
  • The low-affinity NGFR has been shown to have structural homology with another specific B cell surface molecule, CD40, which plays an important role in IgE production [40].
  • No differences in the number of NGF-R mRNA-positive neurons between normal aged and AD patients were detected within the NGF-responsive cell groups of the medial septum (Ch1) and nucleus of the vertical limb of the diagonal band (Ch2) [4].

Analytical, diagnostic and therapeutic context of NGFR

  • METHODS: CD34+CK7/8+ cells from midgestation livers were analyzed for the expression of various markers by flow cytometry and isolated based on their expression of CD34, nerve growth factor receptor (NGFR) and lack of CD45 expression [41].
  • Immunofluorescence studies here showed that NGFR are also present on a proportion of human peripheral blood mononuclear cells (PBMC) [42].
  • Northern blot and ligand binding/immunoprecipitation assays revealed four receptor-positive cell lines (NGP, NLF, SK-N-SH, and LA-N-6), with NGFR mRNA and protein of expected sizes (3.8 kilobases and Mr approximately 75,000, respectively) [43].
  • Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes [43].
  • We report here on the demonstration of NGFR-like proteins from PC12 and SY5Y cells by sequential lectin chromatography, reverse-phase HPLC, and SDS-PAGE analysis of immunoprecipitates obtained with NGFR-specific monoclonal antibodies [25].


  1. Introduction of nerve growth factor (NGF) receptors into a medulloblastoma cell line results in expression of high- and low-affinity NGF receptors but not NGF-mediated differentiation. Pleasure, S.J., Reddy, U.R., Venkatakrishnan, G., Roy, A.K., Chen, J., Ross, A.H., Trojanowski, J.Q., Pleasure, D.E., Lee, V.M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA. Matsushima, H., Bogenmann, E. Mol. Cell. Biol. (1990) [Pubmed]
  3. Nerve growth factor receptor expression in peripheral and central neuroectodermal tumors, other pediatric brain tumors, and during development of the adrenal gland. Baker, D.L., Molenaar, W.M., Trojanowski, J.Q., Evans, A.E., Ross, A.H., Rorke, L.B., Packer, R.J., Lee, V.M., Pleasure, D. Am. J. Pathol. (1991) [Pubmed]
  4. NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer's disease. Higgins, G.A., Mufson, E.J. Exp. Neurol. (1989) [Pubmed]
  5. Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease. Mufson, E.J., Kordower, J.H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  6. A missense polymorphism (S205L) of the low-affinity neurotrophin receptor p75NTR gene is associated with depressive disorder and attempted suicide. Kunugi, H., Hashimoto, R., Yoshida, M., Tatsumi, M., Kamijima, K. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  7. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Loetscher, H., Pan, Y.C., Lahm, H.W., Gentz, R., Brockhaus, M., Tabuchi, H., Lesslauer, W. Cell (1990) [Pubmed]
  8. Expression and structure of the human NGF receptor. Johnson, D., Lanahan, A., Buck, C.R., Sehgal, A., Morgan, C., Mercer, E., Bothwell, M., Chao, M. Cell (1986) [Pubmed]
  9. Induction of apoptosis by the low-affinity NGF receptor. Rabizadeh, S., Oh, J., Zhong, L.T., Yang, J., Bitler, C.M., Butcher, L.L., Bredesen, D.E. Science (1993) [Pubmed]
  10. Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities. Li, B.Q., Kaplan, D., Kung, H.F., Kamata, T. Science (1992) [Pubmed]
  11. Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation. Yan, H., Schlessinger, J., Chao, M.V. Science (1991) [Pubmed]
  12. Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the invasive capability of prostate cancer cells in vitro. Festuccia, C., Muzi, P., Gravina, G.L., Millimaggi, D., Speca, S., Dolo, V., Ricevuto, E., Vicentini, C., Bologna, M. Int. J. Oncol. (2007) [Pubmed]
  13. Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations. Strobach, R.S., Nakamine, H., Masih, A.S., Linder, J., Weisenburger, D.D. Hum. Pathol. (1991) [Pubmed]
  14. Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor. Taglialatela, G., Angelucci, L., Ramacci, M.T., Werrbach-Perez, K., Jackson, G.R., Perez-Polo, J.R. Brain Res. Dev. Brain Res. (1991) [Pubmed]
  15. Expression of immunoreactivities to 75 kDa nerve growth factor receptor, trk gene product and phosphotyrosine in granular cell tumors. Hoshi, N., Tsu-ura, Y., Watanabe, K., Suzuki, T., Kasukawa, R., Suzuki, T. Pathol. Int. (1995) [Pubmed]
  16. Estrogen differentially regulates estrogen and nerve growth factor receptor mRNAs in adult sensory neurons. Sohrabji, F., Miranda, R.C., Toran-Allerand, C.D. J. Neurosci. (1994) [Pubmed]
  17. Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus. Pavelitz, T., Rusché, L., Matera, A.G., Scharf, J.M., Weiner, A.M. EMBO J. (1995) [Pubmed]
  18. Characterization of two neuroblastoma cell lines expressing recombinant nerve growth factor receptors. Reddy, U.R., Venkatakrishnan, G., Roy, A.K., Chen, J., Hardy, M., Mavilio, F., Rovera, G., Pleasure, D., Ross, A.H. J. Neurochem. (1991) [Pubmed]
  19. Immunohistochemistry study of human vestibular nerve schwannoma differentiation. Hung, G., Colton, J., Fisher, L., Oppenheimer, M., Faudoa, R., Slattery, W., Linthicum, F. Glia (2002) [Pubmed]
  20. alpha(2)-Adrenergic receptors activate MAPK and Akt through a pathway involving arachidonic acid metabolism by cytochrome P450-dependent epoxygenase, matrix metalloproteinase activation and subtype-specific transactivation of EGFR. Karkoulias, G., Mastrogianni, O., Lymperopoulos, A., Paris, H., Flordellis, C. Cell. Signal. (2006) [Pubmed]
  21. Nerve growth factor triggers microfilament assembly and paxillin phosphorylation in human B lymphocytes. Melamed, I., Turner, C.E., Aktories, K., Kaplan, D.R., Gelfand, E.W. J. Exp. Med. (1995) [Pubmed]
  22. C-Peptide reverses nociceptive neuropathy in type 1 diabetes. Kamiya, H., Zhang, W., Ekberg, K., Wahren, J., Sima, A.A. Diabetes (2006) [Pubmed]
  23. Effects of NGF and glucocorticoid on NGF receptor immunolabeling of cultured rhesus adrenal chromaffin cells. Herman, M.A., Schulz, C.A., Claude, P. Exp. Cell Res. (1992) [Pubmed]
  24. Expression of human nerve growth factor receptor on cells derived from all three germ layers. Thomson, T.M., Rettig, W.J., Chesa, P.G., Green, S.H., Mena, A.C., Old, L.J. Exp. Cell Res. (1988) [Pubmed]
  25. Reverse-phase high-performance liquid chromatography of nerve growth factor receptor-like proteins identified with monoclonal antibodies. Shan, D.E., Beck, C.E., Werrbach-Perez, K., Perez-Polo, J.R. J. Neurosci. Res. (1990) [Pubmed]
  26. Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue. Reis-Filho, J.S., Steele, D., Di Palma, S., Jones, R.L., Savage, K., James, M., Milanezi, F., Schmitt, F.C., Ashworth, A. Mod. Pathol. (2006) [Pubmed]
  27. Basic fibroblast growth factor enhances nerve growth factor receptor gene promoter activity in human neuroblastoma cell line CHP100. Taiji, M., Taiji, K., Deyerle, K.L., Bothwell, M. Mol. Cell. Biol. (1992) [Pubmed]
  28. Glomerular filtration rate in children: validation and longitudinal use of determination from the 99mTc DTPA renogram. Shore, R.M., Koff, S.A., Hayes, J.R., Smith, S.P., Mentser, M., Mahan, J.D. Am. J. Kidney Dis. (1986) [Pubmed]
  29. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Rodriguez-Tébar, A., Dechant, G., Barde, Y.A. Neuron (1990) [Pubmed]
  30. The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA. Ross, A.H., Daou, M.C., McKinnon, C.A., Condon, P.J., Lachyankar, M.B., Stephens, R.M., Kaplan, D.R., Wolf, D.E. J. Cell Biol. (1996) [Pubmed]
  31. Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson's disease: reduced cell numbers and co-localization with cholinergic neurons. Mufson, E.J., Presley, L.N., Kordower, J.H. Brain Res. (1991) [Pubmed]
  32. Activated transcription of the human neuropeptide Y gene in differentiating SH-SY5Y neuroblastoma cells is dependent on transcription factors AP-1, AP-2alpha, and NGFI. Wernersson, J., Johansson, I., Larsson, U., Minth-Worby, C., Påhlman, S., Andersson, G. J. Neurochem. (1998) [Pubmed]
  33. Reduction of nerve growth factor receptor immunoreactivity in ischaemic gerbil hippocampal CA1 neurons after treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). Lee, T.H., Abe, K., Nakamura, M., Kogure, K., Itoyama, Y. Neurol. Res. (1994) [Pubmed]
  34. Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma. Davidson, B., Reich, R., Lazarovici, P., Flørenes, V.A., Risberg, B., Nielsen, S., Sert, B., Bedrossian, C. Lung Cancer (2004) [Pubmed]
  35. Telomerase activity in a specific cell subset co-expressing integrinbeta1/EGFR but not p75NGFR/bcl2/integrin beta4 in normal human epithelial cells. Kunimura, C., Kikuchi, K., Ahmed, N., Shimizu, A., Yasumoto, S. Oncogene (1998) [Pubmed]
  36. Evidence for the presence of nerve growth factor (NGF) and NGF receptors in human testis. Seidl, K., Holstein, A.F. Cell Tissue Res. (1990) [Pubmed]
  37. Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro. Cattoretti, G., Schiró, R., Orazi, A., Soligo, D., Colombo, M.P. Blood (1993) [Pubmed]
  38. CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of Ras in PC12 cells. Matsuda, M., Hashimoto, Y., Muroya, K., Hasegawa, H., Kurata, T., Tanaka, S., Nakamura, S., Hattori, S. Mol. Cell. Biol. (1994) [Pubmed]
  39. Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Apfel, S.C., Wright, D.E., Wiideman, A.M., Dormia, C., Snider, W.D., Kessler, J.A. Mol. Cell. Neurosci. (1996) [Pubmed]
  40. Nerve growth-factor and anti-CD40 provide opposite signals for the production of IgE in interleukin-4-treated lymphocytes. Brodie, C., Oshiba, A., Renz, H., Bradley, K., Gelfand, E.W. Eur. J. Immunol. (1996) [Pubmed]
  41. Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells. Suskind, D.L., Muench, M.O. J. Hepatol. (2004) [Pubmed]
  42. Expression of nerve growth factor receptors by human peripheral blood mononuclear cells. Morgan, B., Thorpe, L.W., Marchetti, D., Perez-Polo, J.R. J. Neurosci. Res. (1989) [Pubmed]
  43. Multiple defects of the nerve growth factor receptor in human neuroblastomas. Azar, C.G., Scavarda, N.J., Reynolds, C.P., Brodeur, G.M. Cell Growth Differ. (1990) [Pubmed]
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