Lineage-specific signaling in melanocytes. c-Kit stimulation recruits p300/CBP to microphthalmia

E. Roydon Price, Han Fei Ding, Tina Badalian, Shoumo Bhattacharya, Clifford M Takemoto, Tso Pang Yao, Timothy J. Hemesath, David E. Fisher

Research output: Contribution to journalArticlepeer-review

161 Scopus citations


During melanocyte development, the cytokine Steel factor activates its receptor c-Kit, initiating a signal transduction cascade, which is vital for lineage determination via unknown downstream nuclear targets. c-Kit has recently been found to trigger mitogen-activated protein kinase-mediated phosphorylation of Microphthalmia (Mi), a lineage-restricted transcription factor, which, like steel facto and c-Kit, is essential for melanocyte development. This cascade results in increased Mi-dependent tanscriptional reported activity. Here we examine the mechanism by which Mi is activated by this pathway. Phosphorylation does not significantly alter Mi's nuclear localization, DNa binding, or dimerization. However, the tanscriptional coactivator p300/CBP selectively associates with mitogen-activated protein kinase-phosphorylated Mi, even under conditions in which non-MAPK phospho-Mi is more abundant. Moreover, p300/CBP coactivates Mi transcriptional activity in a manner dependent upon this phosphorylation. Mi thus joins CREB as a transcription factor whose signal-responsive phosphorylation regulates coactivator recruitment, in this case modulating lineage development in melanocytes.

Original languageEnglish (US)
Pages (from-to)17983-17986
Number of pages4
JournalJournal of Biological Chemistry
Issue number29
StatePublished - Jul 17 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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