Journal
EMBO JOURNAL
Volume 20, Issue 8, Pages 1921-1930Publisher
OXFORD UNIV PRESS
DOI: 10.1093/emboj/20.8.1921
Keywords
AKAP; cAMP; phosphodiesterase; PKA; signal transduction
Categories
Funding
- Intramural NIH HHS [Z01 HL004229] Funding Source: Medline
- NHLBI NIH HHS [K08 HL004229] Funding Source: Medline
- NIDDK NIH HHS [P01 DK054441, DK54441] Funding Source: Medline
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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.
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