mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module

Kimberly L. Dodge, Samone Khouangsathiene, Michael S. Kapiloff, Robert Mouton, Elaine V. Hill, Miles D. Houslay, Lorene K. Langeberg, John D. Scott

Research output: Contribution to journalArticlepeer-review

378 Scopus citations


Spatiotemporal regulation of protein kinase A (PKA) activity involves the manipulation of compartmentalized cAMP pools. Now we demonstrate that the muscle-selective A-kinase anchoring protein, mAKAP, maintains a cAMP signaling module, including PKA and the rolipram-inhibited cAMP-specific phosphodiesterase (PDE4D3) in heart tissues. Functional analyses indicate that tonic PDE4D3 activity reduces the activity of the anchored PKA holoenzyme, whereas kinase activation stimulates mAKAP-associated phosphodiesterase activity. Disruption of PKA-mAKAP interaction prevents this enhancement of PDE4D3 activity, suggesting that the proximity of both enzymes in the mAKAP signaling complex forms a negative feedback loop to restore basal cAMP levels.

Original languageEnglish (US)
Pages (from-to)1921-1930
Number of pages10
JournalEMBO Journal
Issue number8
StatePublished - Apr 17 2001
Externally publishedYes


  • AKAP
  • cAMP
  • Phosphodiesterase
  • PKA
  • Signal transduction

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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