MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes

Timothy J. Hemesath, E. Roydon Price, Clifford M Takemoto, Tina Badalian, David E. Fisher

Research output: Contribution to journalArticle

Abstract

Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel Factor (S1) result in strikingly similar defects in mast cell and melanocyte development. Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with S1 results in activation of MAP kinase, which in turn phosphorylates Mi at a consensus target serine. This phosphorylation upregulates Mi transactivation of the tyrosinase pigmentation gene promoter. In addition to modulating pigment production, such signalling may regulate the expression of genes essential for melanocyte survival and development. The pathway represents a new application of the general MAP kinase machinery in transducing a signal between a tissue-specific receptor at the cell surface and a tissue-specific transcription factor in the nucleus.

Original languageEnglish (US)
Pages (from-to)298-301
Number of pages4
JournalNature
Volume391
Issue number6664
DOIs
StatePublished - Jan 15 1998
Externally publishedYes

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Microphthalmia-Associated Transcription Factor
Microphthalmos
Melanocytes
Phosphotransferases
Cytokine Receptors
Stem Cell Factor
Monophenol Monooxygenase
Germ-Line Mutation
Essential Genes
Pigmentation
Cell Surface Receptors
Mast Cells
Serine
Transcriptional Activation
Melanoma
Transcription Factors
Up-Regulation
Phosphorylation
Ligands
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Hemesath, T. J., Price, E. R., Takemoto, C. M., Badalian, T., & Fisher, D. E. (1998). MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. Nature, 391(6664), 298-301. https://doi.org/10.1038/34681

MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. / Hemesath, Timothy J.; Price, E. Roydon; Takemoto, Clifford M; Badalian, Tina; Fisher, David E.

In: Nature, Vol. 391, No. 6664, 15.01.1998, p. 298-301.

Research output: Contribution to journalArticle

Hemesath, TJ, Price, ER, Takemoto, CM, Badalian, T & Fisher, DE 1998, 'MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes', Nature, vol. 391, no. 6664, pp. 298-301. https://doi.org/10.1038/34681
Hemesath TJ, Price ER, Takemoto CM, Badalian T, Fisher DE. MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. Nature. 1998 Jan 15;391(6664):298-301. https://doi.org/10.1038/34681
Hemesath, Timothy J. ; Price, E. Roydon ; Takemoto, Clifford M ; Badalian, Tina ; Fisher, David E. / MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. In: Nature. 1998 ; Vol. 391, No. 6664. pp. 298-301.
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