Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

The role of the low-affinity neurotrophin receptor (p75 NTR ) in signal transduction is undefined. Nerve growth factor can activate the sphingomyelin cycle, generating the putative-lipid second messenger ceramide. In T9 glioma cells, addition of a cell-permeable ceramide analog mimicked the effects of nerve growth factor on cell growth inhibition and process formation. This signaling pathway appears to be mediated by p75 NTR in T9 cells and NIH 3T3 cells overexpressing p75 NTR . Expression of an epidermal growth factor receptor-p75 NTR chimera in T9 cells imparted to epidermal growth factor the ability to activate the sphingomyelin cycle. These data demonstrate that p75 NTR is capable of signaling independently of the trk neurotrophin receptor (p140 trk ) and that ceramide may be a mediator in neurotrophin biology.

Bibliography

Dobrowsky, R. T., Werner, M. H., Castellino, A. M., Chao, M. V., & Hannun, Y. A. (1994). Activation of the Sphingomyelin Cycle Through the Low-Affinity Neurotrophin Receptor. Science, 265(5178), 1596–1599.

Authors 5
  1. Rick T. Dobrowsky (first)
  2. Mark H. Werner (additional)
  3. Alexander M. Castellino (additional)
  4. Moses V. Chao (additional)
  5. Yusuf A. Hannun (additional)
References 45 Referenced 483
  1. ANTON, E.S., NERVE GROWTH-FACTOR AND ITS LOW-AFFINITY RECEPTOR PROMOTE SCHWANN-CELL MIGRATION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 91: 2795 (1994). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1994)
  2. BALLOU, L.R., INTERLEUKIN-1-MEDIATED PGE2 PRODUCTION AND SPHINGOMYELIN METABOLISM - EVIDENCE FOR THE REGULATION OF CYCLOOXYGENASE GENE-EXPRESSION BY SPHINGOSINE AND CERAMIDE, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 20044 (1992). (10.1016/S0021-9258(19)88663-5) / JOURNAL OF BIOLOGICAL CHEMISTRY (1992)
  3. BARRETT, G.L., THE P75 NERVE GROWTH-FACTOR RECEPTOR MEDIATES SURVIVAL OR DEATH DEPENDING ON THE STAGE OF SENSORY NEURON DEVELOPMENT, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 91: 6501 (1994). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1994)
  4. BENEDETTI, M, DIFFERENTIAL EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS LEADS TO ALTERED BINDING-AFFINITY AND NEUROTROPHIN RESPONSIVENESS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 7859 (1993). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1993)
  5. 10.1126/science.1321502
  6. CORDONCARDO, C, THE TRK TYROSINE PROTEIN-KINASE MEDIATES THE MITOGENIC PROPERTIES OF NERVE GROWTH-FACTOR AND NEUROTROPHIN-3, CELL 66: 173 (1991). (10.1016/0092-8674(91)90149-S) / CELL (1991)
  7. DOBROWSKY, R.T., CERAMIDE STIMULATES A CYTOSOLIC PROTEIN PHOSPHATASE, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 5048 (1992). (10.1016/S0021-9258(18)42727-5) / JOURNAL OF BIOLOGICAL CHEMISTRY (1992)
  8. DOBROWSKY, R.T., CERAMIDE ACTIVATES HETEROTRIMERIC PROTEIN PHOSPHATASE-2A, JOURNAL OF BIOLOGICAL CHEMISTRY 268: 15523 (1993). (10.1016/S0021-9258(18)82288-8) / JOURNAL OF BIOLOGICAL CHEMISTRY (1993)
  9. DOBROWSKY R.T. unpublished data.
  10. ERNFORS, P, DEMENTIA 1: 138 (1990). / DEMENTIA (1990)
  11. FEINSTEIN, D.L., IDENTIFICATION OF A CONSERVED PROTEIN MOTIF IN A GROUP OF GROWTH-FACTOR RECEPTORS, FEBS LETTERS 272: 7 (1990). (10.1016/0014-5793(90)80437-N) / FEBS LETTERS (1990)
  12. GROB, P.M., CHARACTERIZATION OF THE HUMAN-MELANOMA NERVE GROWTH-FACTOR RECEPTOR, JOURNAL OF BIOLOGICAL CHEMISTRY 260: 8044 (1985). (10.1016/S0021-9258(17)39561-3) / JOURNAL OF BIOLOGICAL CHEMISTRY (1985)
  13. HANNUN, Y.A., SPHINGOLIPID BREAKDOWN PRODUCTS - ANTIPROLIFERATIVE AND TUMOR-SUPPRESSOR LIPIDS, BIOCHIMICA ET BIOPHYSICA ACTA 1154: 223 (1993). (10.1016/0304-4157(93)90001-5) / BIOCHIMICA ET BIOPHYSICA ACTA (1993)
  14. HEMPSTEAD, B.L., DELETION OF CYTOPLASMIC SEQUENCES OF THE NERVE GROWTH-FACTOR RECEPTOR LEADS TO LOSS OF HIGH-AFFINITY LIGAND-BINDING, JOURNAL OF BIOLOGICAL CHEMISTRY 265: 9595 (1990). (10.1016/S0021-9258(19)38707-1) / JOURNAL OF BIOLOGICAL CHEMISTRY (1990)
  15. 10.1038/350678a0
  16. HERMANN, J.L., MOL BIOL CELL 4: 1205 (1993). (10.1091/mbc.4.11.1205) / MOL BIOL CELL (1993)
  17. JAYADEV, S, IDENTIFICATION OF ARACHIDONIC-ACID AS A MEDIATOR OF SPHINGOMYELIN HYDROLYSIS IN RESPONSE TO TUMOR-NECROSIS-FACTOR-ALPHA, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 5757 (1994). (10.1016/S0021-9258(17)37526-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1994)
  18. 10.1016/0896-6273(92)90066-M
  19. JOHNSON, D, EXPRESSION AND STRUCTURE OF THE HUMAN NGF RECEPTOR, CELL 47: 545 (1986). (10.1016/0092-8674(86)90619-7) / CELL (1986)
  20. KAHLE, P, NERVE GROWTH-FACTOR (NGF) RECEPTOR ON RAT GLIAL-CELL LINES - EVIDENCE FOR NGF INTERNALIZATION VIA P75(NGFR), JOURNAL OF BIOLOGICAL CHEMISTRY 267: 13917 (1992). (10.1016/S0021-9258(19)49656-7) / JOURNAL OF BIOLOGICAL CHEMISTRY (1992)
  21. 10.1126/science.1850549
  22. KIM, M.Y., IDENTIFICATION OF SPHINGOMYELIN TURNOVER AS AN EFFECTOR MECHANISM FOR THE ACTION OF TUMOR-NECROSIS-FACTOR-ALPHA AND GAMMA-INTERFERON - SPECIFIC ROLE IN CELL-DIFFERENTIATION, JOURNAL OF BIOLOGICAL CHEMISTRY 266: 484 (1991). (10.1016/S0021-9258(18)52461-3) / JOURNAL OF BIOLOGICAL CHEMISTRY (1991)
  23. KLEIN, R, THE TRK PROTOONCOGENE ENCODES A RECEPTOR FOR NERVE GROWTH-FACTOR, CELL 65: 189 (1991). (10.1016/0092-8674(91)90419-Y) / CELL (1991)
  24. 10.1126/science.3306916
  25. MAHADEO, D, HIGH-AFFINITY NERVE GROWTH-FACTOR BINDING DISPLAYS A FASTER RATE OF ASSOCIATION THAN P140(TRK) BINDING - IMPLICATIONS FOR MULTISUBUNIT POLYPEPTIDE RECEPTORS, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 6884 (1994). (10.1016/S0021-9258(17)37458-6) / JOURNAL OF BIOLOGICAL CHEMISTRY (1994)
  26. MARUSHIGE, Y, MODULATION OF GROWTH AND OF MORPHOLOGICAL-CHARACTERISTICS IN GLIOMA-CELLS BY NERVE GROWTH-FACTOR AND GLIA MATURATION FACTOR, CANCER RESEARCH 47: 4109 (1987). / CANCER RESEARCH (1987)
  27. MATHIAS, S, CHARACTERIZATION OF A CERAMIDE-ACTIVATED PROTEIN-KINASE - STIMULATION BY TUMOR-NECROSIS-FACTOR-ALPHA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 10009 (1991). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1991)
  28. MATHIAS, S, ACTIVATION OF THE SPHINGOMYELIN SIGNALING PATHWAY IN INTACT EL4 CELLS AND IN A CELL-FREE SYSTEM BY IL-1-BETA, SCIENCE 259: 519 (1993). (10.1126/science.8424175) / SCIENCE (1993)
  29. MEAKIN, S.O., MOLECULAR INVESTIGATIONS ON THE HIGH-AFFINITY NERVE GROWTH-FACTOR RECEPTOR, NEURON 6: 153 (1991). (10.1016/0896-6273(91)90130-R) / NEURON (1991)
  30. 10.1126/science.8456305
  31. OHMICHI, M, NERVE GROWTH-FACTOR INDUCES THE ASSOCIATION OF A 130-KD PHOSPHOPROTEIN WITH ITS RECEPTOR IN PC-12 PHEOCHROMOCYTOMA CELLS, CELL REGULATION 2: 691 (1991). (10.1091/mbc.2.9.691) / CELL REGULATION (1991)
  32. OKAZAKI, T, SPHINGOMYELIN TURNOVER INDUCED BY VITAMIN-D3 IN HL-60 CELLS - ROLE IN CELL-DIFFERENTIATION, JOURNAL OF BIOLOGICAL CHEMISTRY 264: 19076 (1989). (10.1016/S0021-9258(19)47268-2) / JOURNAL OF BIOLOGICAL CHEMISTRY (1989)
  33. OKAZAKI, T, ROLE OF CERAMIDE AS A LIPID MEDIATOR OF 1-ALPHA,25-DIHYDROXYVITAMIN-D3-INDUCED HL-60 CELL-DIFFERENTIATION, JOURNAL OF BIOLOGICAL CHEMISTRY 265: 15823 (1990). (10.1016/S0021-9258(18)55472-7) / JOURNAL OF BIOLOGICAL CHEMISTRY (1990)
  34. OLIVERA, A, SPHINGOMYELINASE AND CELL-PERMEABLE CERAMIDE ANALOGS STIMULATE CELLULAR PROLIFERATION IN QUIESCENT SWISS-3T3 FIBROBLASTS, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 26121 (1992). (10.1016/S0021-9258(18)35725-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1992)
  35. 10.1126/science.8332899
  36. RADEKE, M.J., GENE-TRANSFER AND MOLECULAR-CLONING OF THE RAT NERVE GROWTH-FACTOR RECEPTOR, NATURE 325: 593 (1987). (10.1038/325593a0) / NATURE (1987)
  37. REPRESA, J, GLYCOSYL-PHOSPHATIDYLINOSITOL INOSITOL PHOSPHOGLYCAN - A SIGNALING SYSTEM FOR THE LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 8016 (1991). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1991)
  38. RODRIGUEZTEBAR, A, BINDING OF NEUROTROPHIN-3 TO ITS NEURONAL RECEPTORS AND INTERACTIONS WITH NERVE GROWTH-FACTOR AND BRAIN-DERIVED NEUROTROPHIC FACTOR, EMBO JOURNAL 11: 917 (1992). (10.1002/j.1460-2075.1992.tb05130.x) / EMBO JOURNAL (1992)
  39. SMITH, C.A., THE TNF RECEPTOR SUPERFAMILY OF CELLULAR AND VIRAL-PROTEINS - ACTIVATION, COSTIMULATION, AND DEATH, CELL 76: 959 (1994). (10.1016/0092-8674(94)90372-7) / CELL (1994)
  40. 10.1126/science.2160731
  41. TANIUCHI, M, EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS BY SCHWANN-CELLS OF AXOTOMIZED PERIPHERAL-NERVES - ULTRASTRUCTURAL LOCATION, SUPPRESSION BY AXONAL CONTACT, AND BINDING-PROPERTIES, JOURNAL OF NEUROSCIENCE 8: 664 (1988). (10.1523/JNEUROSCI.08-02-00664.1988) / JOURNAL OF NEUROSCIENCE (1988)
  42. VANVELDHOVEN, P.P., CHANGES IN BIOACTIVE LIPIDS, ALKYLACYLGLYCEROL AND CERAMIDE, OCCUR IN HIV-INFECTED CELLS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 187: 209 (1992). (10.1016/S0006-291X(05)81480-9) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1992)
  43. VOLONTE, C, ASSOCIATION OF PROTEIN-KINASES ERK1 AND ERK2 WITH P75 NERVE GROWTH-FACTOR RECEPTORS, JOURNAL OF BIOLOGICAL CHEMISTRY 268: 21410 (1993). (10.1016/S0021-9258(19)36939-X) / JOURNAL OF BIOLOGICAL CHEMISTRY (1993)
  44. VONBARTHELD, C.S., POSITIVE AND NEGATIVE EFFECTS OF NEUROTROPHINS ON THE ISTHMO-OPTIC NUCLEUS IN CHICK-EMBRYOS, NEURON 12: 639 (1994). (10.1016/0896-6273(94)90219-4) / NEURON (1994)
  45. 10.1126/science.1850551
Dates
Type When
Created 18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.)
Deposited 1 year, 7 months ago (Jan. 14, 2024, 10:52 p.m.)
Indexed 2 weeks, 6 days ago (Aug. 5, 2025, 9:12 a.m.)
Issued 30 years, 11 months ago (Sept. 9, 1994)
Published 30 years, 11 months ago (Sept. 9, 1994)
Published Print 30 years, 11 months ago (Sept. 9, 1994)
Funders 0

None

@article{Dobrowsky_1994, title={Activation of the Sphingomyelin Cycle Through the Low-Affinity Neurotrophin Receptor}, volume={265}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.8079174}, DOI={10.1126/science.8079174}, number={5178}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Dobrowsky, Rick T. and Werner, Mark H. and Castellino, Alexander M. and Chao, Moses V. and Hannun, Yusuf A.}, year={1994}, month=sep, pages={1596–1599} }