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 journalArticle

358 Citations (Scopus)

Abstract

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
Pages (from-to)1921-1930
Number of pages10
JournalEMBO Journal
Volume20
Issue number8
DOIs
StatePublished - Apr 17 2001
Externally publishedYes

Fingerprint

Type 4 Cyclic Nucleotide Phosphodiesterase
Cyclic AMP-Dependent Protein Kinases
Phosphotransferases
Rolipram
Holoenzymes
Phosphoric Diester Hydrolases
Protein Kinases
Muscle
Chemical activation
Tissue
Feedback
Muscles
Enzymes
Proteins

Keywords

  • AKAP
  • cAMP
  • Phosphodiesterase
  • PKA
  • Signal transduction

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Dodge, K. L., Khouangsathiene, S., Kapiloff, M. S., Mouton, R., Hill, E. V., Houslay, M. D., ... Scott, J. D. (2001). mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO Journal, 20(8), 1921-1930. https://doi.org/10.1093/emboj/20.8.1921

mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. / Dodge, Kimberly L.; Khouangsathiene, Samone; Kapiloff, Michael S; Mouton, Robert; Hill, Elaine V.; Houslay, Miles D.; Langeberg, Lorene K.; Scott, John D.

In: EMBO Journal, Vol. 20, No. 8, 17.04.2001, p. 1921-1930.

Research output: Contribution to journalArticle

Dodge, KL, Khouangsathiene, S, Kapiloff, MS, Mouton, R, Hill, EV, Houslay, MD, Langeberg, LK & Scott, JD 2001, 'mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module', EMBO Journal, vol. 20, no. 8, pp. 1921-1930. https://doi.org/10.1093/emboj/20.8.1921
Dodge KL, Khouangsathiene S, Kapiloff MS, Mouton R, Hill EV, Houslay MD et al. mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO Journal. 2001 Apr 17;20(8):1921-1930. https://doi.org/10.1093/emboj/20.8.1921
Dodge, Kimberly L. ; Khouangsathiene, Samone ; Kapiloff, Michael S ; Mouton, Robert ; Hill, Elaine V. ; Houslay, Miles D. ; Langeberg, Lorene K. ; Scott, John D. / mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. In: EMBO Journal. 2001 ; Vol. 20, No. 8. pp. 1921-1930.
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