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PMID: 11296225 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 20 ·No. 8 ·2001-04-17 ·Pages 1921-30

Dodge KL, Khouangsathiene S, Kapiloff MS, Mouton R, Hill EV, Houslay MD, Langeberg LK, Scott JD

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.

MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases/metabolism Animals Cells, Cultured Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Cyclic Nucleotide Phosphodiesterases, Type 4 Feedback Heart Ventricles/cytology,metabolism Models, Biological Muscle Proteins/metabolism Myocardium/cytology,metabolism Protein Binding Rats Signal Transduction
Chemicals
Muscle Proteins Cyclic AMP Cyclic AMP-Dependent Protein Kinases 3',5'-Cyclic-AMP Phosphodiesterases Cyclic Nucleotide Phosphodiesterases, Type 4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Dodge K L
Howard Hughes Medical Institute and Vollum Institute, and Department of Pediatrics, Oregon Health Sciences University, Portland, OR 97201-3098, USA.
Khouangsathiene S
Kapiloff M S
Mouton R
Hill E V
Houslay M D
Langeberg L K
Scott J D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.8.1921
Published
2001-04-17
Pages
1921-30
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125429
Subset
IM
Grants
NHLBI NIH HHS · K08 HL004229 · United States
NIDDK NIH HHS · P01 DK054441 · United States
Intramural NIH HHS · Z01 HL004229 · United States
NIDDK NIH HHS · DK54441 · United States
External Links
PubMed source DOI: 10.1093/emboj/20.8.1921 PMC Full Text View journal details
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