Cyclic AMP-dependent protein kinase inhibits the activity of myogenic helix-loop-helix proteins

Li Li, Robin Heller-Harrison, Michael Czech, Eric N. Olson

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Differentiation of skeletal muscle cells is inhibited by the cyclic AMP (cAMP) signal transduction pathway. Here we report that the catalytic subunit of cAMP-dependent protein kinase (PKA) can substitute for cAMP and suppress muscle-specific transcription by silencing the activity of the MyoD family of regulatory factors, which includes MyoD, myogenin, myf5, and MRF4. Repression by the PKA catalytic (C) subunit is directed at the consensus sequence CANNTG, the target for DNA binding and transcriptional activation by these myogenic regulators. Phosphopeptide mapping of myogenin in vitro and in vivo revealed two PKA phosphorylation sites, both within the basic region. However, repression of myogenin function by PKA does not require direct phosphorylation of these sites but instead involves an indirect mechanism with one or more intermediate steps. Regulation of the transcriptional activity of the MyoD family by modulation of the cAMP signaling pathway may account for the inhibitory effects of certain peptide growth factors on muscle-specific gene expression and may also determine the responsiveness of different cell types to myogenic conversion by these myogenic regulators.

Original languageEnglish (US)
Pages (from-to)4478-4485
Number of pages8
JournalMolecular and cellular biology
Volume12
Issue number10
DOIs
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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