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PMID: 7929831 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes.

The Journal of clinical investigation ·Vol. 94 ·No. 4 ·1994-10-00 ·Pages 1550-62

Yaar M, Eller MS, DiBenedetto P, Reenstra WR, Zhai S, McQuaid T, Archambault M, Gilchrest BA

Abstract

We have recently shown that (a) human melanocytes express the p75 nerve growth factor (NGF) receptor in vitro; (b) that melanocyte dendricity and migration, among other behaviors, are regulated at least in part by NGF; and (c) that cultured human epidermal keratinocytes produce NGF. We now report that melanocyte stimulation with phorbol 12-tetra decanoate 13-acetate (TPA), previously reported to induce p75 NGF receptor, also induces trk in melanocytes, and TPA effect is further potentiated by the presence of keratinocytes in culture. Moreover, trk in melanocytes becomes phosphorylated within minutes after NGF stimulation. As well, cultures of dermal fibroblasts express neurotrophin-3 (NT-3) mRNA; NT-3 mRNA levels in cultured fibroblasts are modulated by mitogenic stimulation, UV irradiation, and exposure to melanocyte-conditioned medium. Moreover, melanocytes constitutively express low levels of trk-C, and its expression is downregulated after TPA stimulation. NT-3 supplementation to cultured melanocytes maintained in Medium 199 alone prevents cell death. These combined data suggest that melanocyte behavior in human skin may be influenced by neurotrophic factors, possibly of keratinocyte and fibroblast origin, which act through high affinity receptors.

MeSH Terms
Amino Acid Sequence Base Sequence Cell Survival/drug effects Cells, Cultured Cloning, Molecular Fibroblasts/metabolism Gene Expression Regulation/radiation effects Humans Keratinocytes/metabolism Melanocytes/drug effects,metabolism Molecular Sequence Data Nerve Growth Factors/biosynthesis,genetics,metabolism,pharmacology Neurotrophin 3 Phosphorylation Proto-Oncogene Proteins/biosynthesis,genetics RNA, Messenger/analysis Receptor Protein-Tyrosine Kinases/biosynthesis,genetics,metabolism Receptor, trkA Receptors, Nerve Growth Factor/biosynthesis,genetics Sequence Analysis, DNA Skin/cytology Tetradecanoylphorbol Acetate/pharmacology Tumor Cells, Cultured Ultraviolet Rays
Chemicals
Nerve Growth Factors Neurotrophin 3 Proto-Oncogene Proteins RNA, Messenger Receptors, Nerve Growth Factor Receptor Protein-Tyrosine Kinases Receptor, trkA Tetradecanoylphorbol Acetate
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yaar M
Department of Dermatology, Boston University School of Medicine, Massachusetts 02118.
Eller M S
DiBenedetto P
Reenstra W R
Zhai S
McQuaid T
Archambault M
Gilchrest B A
References (73)
73 references, click to expand
  1. trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development.
    EMBO J. 1989 Dec 1;8(12):3701-9 PMID: 2555172
  2. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3.
    Cell. 1991 Sep 6;66(5):967-79 PMID: 1653651
  3. Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations.
    Genomics. 1991 Jul;10(3):558-68 PMID: 1889806
  4. Evidence for nerve growth factor-mediated paracrine effects in human epidermis.
    J Cell Biol. 1991 Nov;115(3):821-8 PMID: 1655813
  5. Protein kinase C-induced redistribution of the cytoskeleton and phosphorylation of vimentin in cultured brain macrophages.
    J Neurosci Res. 1991 Jul;29(3):362-78 PMID: 1920533
  6. Growth-regulated synthesis and secretion of biologically active nerve growth factor by human keratinocytes.
    J Biol Chem. 1991 Nov 15;266(32):21718-22 PMID: 1718982
  7. Human melanocyte growth and differentiation: a decade of new data.
    J Invest Dermatol. 1991 Oct;97(4):611-7 PMID: 1940431
  8. Pigment content of cultured human melanocytes does not correlate with tyrosinase message level.
    Br J Dermatol. 1991 Oct;125(4):297-303 PMID: 1720016
  9. Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):648-52 PMID: 1731336
  10. Hormone- and phorbol ester-activated protein kinase C isozymes mediate a reorganization of the actin cytoskeleton associated with prolactin secretion in GH4C1 cells.
    Mol Endocrinol. 1992 Jan;6(1):120-31 PMID: 1738365
  11. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family.
    Nature. 1990 Mar 22;344(6264):339-41 PMID: 2314473
  12. Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212).
    J Clin Invest. 1990 Apr;85(4):1085-9 PMID: 2318966
  13. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF.
    Science. 1990 Mar 23;247(4949 Pt 1):1446-51 PMID: 2321006
  14. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor.
    Neuron. 1990 Apr;4(4):487-92 PMID: 2157470
  15. Primary structure and biological activity of a novel human neurotrophic factor.
    Neuron. 1990 May;4(5):767-73 PMID: 2344409
  16. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain.
    Cell. 1990 May 18;61(4):647-56 PMID: 2160854
  17. Expression of the trk proto-oncogene is restricted to the sensory cranial and spinal ganglia of neural crest origin in mouse development.
    Genes Dev. 1990 May;4(5):683-94 PMID: 2379826
  18. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression.
    Neuron. 1990 Oct;5(4):501-9 PMID: 1688327
  19. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family.
    Neuron. 1990 Oct;5(4):511-26 PMID: 2206535
  20. Dissociation of proto-oncogene induction from growth response in normal human fibroblasts.
    J Cell Physiol. 1990 Oct;145(1):39-45 PMID: 2120243
  21. Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system.
    Development. 1990 Aug;109(4):845-50 PMID: 2171894
  22. Molecular cloning of a human gene that is a member of the nerve growth factor family.
    Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060-4 PMID: 2236018
  23. trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors.
    Mol Cell Biol. 1991 Jan;11(1):143-53 PMID: 1846020
  24. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF.
    Nature. 1991 Mar 14;350(6314):158-60 PMID: 1706478
  25. Parkinson's disease. Fresh factors to consider.
    Nature. 1991 Mar 21;350(6315):195 PMID: 2005976
  26. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor.
    Science. 1991 Apr 26;252(5005):554-8 PMID: 1850549
  27. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor.
    Nature. 1991 Apr 25;350(6320):678-83 PMID: 1850821
  28. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary.
    Neuron. 1991 May;6(5):845-58 PMID: 2025430
  29. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor.
    Cell. 1991 May 31;65(5):895-903 PMID: 1645620
  30. Keeping track of neurotrophin receptors.
    Cell. 1991 Jun 14;65(6):915-8 PMID: 1646079
  31. Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-gamma 1 by a kinase activity associated with the product of the trk protooncogene.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5650-4 PMID: 1712104
  32. The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3.
    Cell. 1991 Jul 12;66(1):173-83 PMID: 1649007
  33. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.
    Cell. 1991 Jul 26;66(2):395-403 PMID: 1649702
  34. NGF in CNS: experimental data and clinical implications.
    Prog Growth Factor Res. 1989;1(3):143-59 PMID: 2562358
  35. Embryonic corneal epithelial actin alters distribution in response to laminin.
    Invest Ophthalmol Vis Sci. 1992 Feb;33(2):324-33 PMID: 1740362
  36. Intracellular localization of types I and II collagen mRNA and endoplasmic reticulum in embryonic corneal epithelia.
    J Cell Sci. 1991 Sep;100 ( Pt 1):23-33 PMID: 1795029
  37. Neurotrophin 3 is a mitogen for cultured neural crest cells.
    Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1661-5 PMID: 1542658
  38. Protective effect of alpha-tocopherol in carrier liposomes on ultraviolet-mediated human epidermal cell damage in vitro.
    Photodermatol Photoimmunol Photomed. 1991 Dec;8(6):236-42 PMID: 1823148
  39. Activation of the c-Raf protein kinase by protein kinase C phosphorylation.
    Oncogene. 1992 Nov;7(11):2259-62 PMID: 1437148
  40. The MARCKS family of cellular protein kinase C substrates.
    J Biol Chem. 1993 Jan 25;268(3):1501-4 PMID: 8420923
  41. Neurotrophin 3 supports the survival of developing muscle sensory neurons in culture.
    Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2613-7 PMID: 8464867
  42. Protein kinase C alpha activates RAF-1 by direct phosphorylation.
    Nature. 1993 Jul 15;364(6434):249-52 PMID: 8321321
  43. The nerve growth factor: thirty-five years later.
    EMBO J. 1987 May;6(5):1145-54 PMID: 3301324
  44. Ultraviolet radiation directly induces pigment production by cultured human melanocytes.
    J Cell Physiol. 1987 Oct;133(1):88-94 PMID: 2822734
  45. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  46. Relationship between actinic damage and chronologic aging in keratinocyte cultures of human skin.
    J Invest Dermatol. 1979 May;72(5):219-23 PMID: 458182
  47. Prior chronic sun exposure decreases the lifespan of human skin fibroblasts in vitro.
    J Gerontol. 1980 Jul;35(4):537-41 PMID: 7400546
  48. Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin.
    Proc Natl Acad Sci U S A. 1982 Mar;79(6):2018-22 PMID: 6952249
  49. Phorbol diester receptor copurifies with protein kinase C.
    Proc Natl Acad Sci U S A. 1983 Jan;80(1):36-40 PMID: 6296873
  50. Transcriptional activation of immunoglobulin alpha heavy-chain genes by translocation of the c-myc oncogene.
    Nature. 1983 Sep 29-Oct 5;305(5933):443-6 PMID: 6413865
  51. Phorbol esters, phospholipase C, and growth factors rapidly stimulate the phosphorylation of a Mr 80,000 protein in intact quiescent 3T3 cells.
    Proc Natl Acad Sci U S A. 1983 Dec;80(23):7244-8 PMID: 6316349
  52. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor.
    Cell. 1983 Dec;35(3 Pt 2):603-10 PMID: 6606489
  53. Purification of a new neurotrophic factor from mammalian brain.
    EMBO J. 1982;1(5):549-53 PMID: 7188352
  54. Turnover of inositol phospholipids and signal transduction.
    Science. 1984 Sep 21;225(4668):1365-70 PMID: 6147898
  55. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene.
    Nature. 1984 Oct 4-10;311(5985):433-8 PMID: 6090941
  56. Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane.
    Nature. 1984 Oct 4-10;311(5985):480-3 PMID: 6090944
  57. Selective cultivation of human melanocytes from newborn and adult epidermis.
    J Invest Dermatol. 1984 Nov;83(5):370-6 PMID: 6491362
  58. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene.
    Nucleic Acids Res. 1985 Apr 11;13(7):2485-502 PMID: 2987855
  59. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences.
    Nature. 1986 Feb 27-Mar 5;319(6056):743-8 PMID: 2869410
  60. Gene transfer and molecular cloning of the human NGF receptor.
    Science. 1986 Apr 25;232(4749):518-21 PMID: 3008331
  61. Protein kinase C activation by diacylglycerol second messengers.
    Cell. 1986 Jun 6;45(5):631-2 PMID: 3708690
  62. Studies and perspectives of protein kinase C.
    Science. 1986 Jul 18;233(4761):305-12 PMID: 3014651
  63. Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity.
    Proc Natl Acad Sci U S A. 1986 Aug;83(16):5822-4 PMID: 3526339
  64. Calcium, cyclic AMP and protein kinase C--partners in mitogenesis.
    Cancer Metastasis Rev. 1987;5(3):205-50 PMID: 3030578
  65. Phosphorylation of ras oncogene product by protein kinase C.
    Biochem Biophys Res Commun. 1987 Jun 15;145(2):782-8 PMID: 3496094
  66. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.
    Mol Cell Biol. 1987 Oct;7(10):3490-502 PMID: 3119989
  67. The physiological function of nerve growth factor in the central nervous system: comparison with the periphery.
    Rev Physiol Biochem Pharmacol. 1987;109:145-78 PMID: 3317757
  68. The expression, localization and functional significance of beta-nerve growth factor in the central nervous system.
    Brain Res. 1987 Nov;434(4):439-64 PMID: 2825921
  69. The melanocyte. Its structure, function, and subpopulations in skin, eyes, and hair.
    Dermatol Clin. 1988 Apr;6(2):161-73 PMID: 3288380
  70. Phosphorylation of neurofilament proteins by protein kinase C.
    FEBS Lett. 1988 Jun 6;233(1):181-5 PMID: 3384089
  71. Induction of nerve growth factor receptors on cultured human melanocytes.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5282-6 PMID: 2839841
  72. Molecular and biochemical characterization of the human trk proto-oncogene.
    Mol Cell Biol. 1989 Jan;9(1):24-33 PMID: 2927393
  73. Molecular cloning and expression of brain-derived neurotrophic factor.
    Nature. 1989 Sep 14;341(6238):149-52 PMID: 2779653
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117496
Published
1994-10-00
Pages
1550-62
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295306
Subset
IM
Grants
NICHD NIH HHS · HD-24538 · United States
External Links
PubMed source DOI: 10.1172/JCI117496 PMC Full Text View journal details
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