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

Cell. 1992 Dec 24;71(7):1181-94. doi: 10.1016/s0092-8674(05)80066-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / physiology
  • Fibroblast Growth Factors / pharmacology*
  • Molecular Sequence Data
  • Muscle Proteins / drug effects*
  • Myogenin
  • Phosphorylation
  • Protein Kinase C / pharmacology*
  • Signal Transduction
  • Trans-Activators
  • Transcription, Genetic / drug effects*


  • Muscle Proteins
  • Myogenin
  • Trans-Activators
  • Fibroblast Growth Factors
  • Protein Kinase C