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PMID: 1328856 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 12 ·No. 10 ·1992-10-00 ·Pages 4478-85

Li L, Heller-Harrison R, Czech M, Olson EN

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.

MeSH Terms
Amino Acid Sequence Cell Differentiation/genetics Cell Line Gene Expression Regulation Molecular Sequence Data Muscle Proteins/antagonists & inhibitors,genetics,metabolism Muscles/cytology,metabolism Mutagenesis, Site-Directed MyoD Protein Myogenin Organ Specificity/genetics Peptide Mapping Phosphorylation Protein Kinases/metabolism Transcription Factors/antagonists & inhibitors,metabolism Transcription, Genetic
Chemicals
Muscle Proteins MyoD Protein Myogenin Transcription Factors Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Li L
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Heller-Harrison R
Czech M
Olson E N
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.10.4478-4485.1992
Published
1992-10-00
Pages
4478-85
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360373
Subset
IM
Grants
NIAMS NIH HHS · AR39848 · United States
NIAMS NIH HHS · AR40339 · United States
NIDDK NIH HHS · DK30648 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.10.4478-4485.1992 PMC Full Text View journal details
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