FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains

Li Li, Jumin Zhou, Guy James, Robin Heller-Harrison, Michael P. Czech, Eric N. Olson

Research output: Contribution to journalArticle

278 Scopus citations

Abstract

Myogenin belongs to a family of myogenic helix-loop-helix (HLH) proteins that activate muscle transcription through binding to a conserved DNA sequence associated with numerous muscle-specific genes. Fibroblast growth factor (FGF) inhibits myogenesis by inactivating myogenic HLH proteins. We show that activated protein kinase C (PKC) can substitute for FGF and inhibit transcriptional activity of myogenic HLH proteins. In transfected cells, FGF induces phosphorylation of a conserved site in the DNA-binding domain of myogenin. This site is phosphorylated by PKC in vivo and in vitro and mediates repression of the myogenic program through a loss in DNA binding activity. A myogenin mutant lacking the PKC phosphorylation site is not repressed by FGF, confirming this site as a molecular target for FGF-dependent repression of muscle transcription. These results establish a direct link between the signal transduction pathways that inhibit myogenesis and the transcription factors directly activating muscle-specific genes.

Original languageEnglish (US)
Pages (from-to)1181-1194
Number of pages14
JournalCell
Volume71
Issue number7
DOIs
StatePublished - Dec 24 1992

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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