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

Author

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  • Timothy J. Hemesath

    (Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School)

  • E. Roydon Price

    (Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School)

  • Clifford Takemoto

    (Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School)

  • Tina Badalian

    (Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School)

  • David E. Fisher

    (Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School)

Abstract

Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel factor (Sl) result in strikingly similar defects in mast cell and melanocyte development1,2,3. Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with Sl 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.

Suggested Citation

  • Timothy J. Hemesath & E. Roydon Price & Clifford Takemoto & Tina Badalian & David E. Fisher, 1998. "MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes," Nature, Nature, vol. 391(6664), pages 298-301, January.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6664:d:10.1038_34681
    DOI: 10.1038/34681
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    1. Pakavarin Louphrasitthiphol & Alessia Loffreda & Vivian Pogenberg & Sarah Picaud & Alexander Schepsky & Hans Friedrichsen & Zhiqiang Zeng & Anahita Lashgari & Benjamin Thomas & E. Elizabeth Patton & M, 2023. "Acetylation reprograms MITF target selectivity and residence time," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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