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

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, Animals, Cells, Cultured, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Cyclic Nucleotide Phosphodiesterases, Type 4, Feedback, Heart Ventricles, Models, Biological, Muscle Proteins, Myocardium, Protein Binding, Rats, Signal Transduction
EMBO J.
Date: Apr. 17, 2001
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