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

Autor: Dodge, Kimberly L., Khouangsathiene, Samone, Kapiloff, Michael S., Mouton, Robert, Hill, Elaine V., Houslay, Miles D., Langeberg, Lorene K., Scott, John D.
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Zdroj: EMBO Journal; 4/15/2001, Vol. 20 Issue 8, p1921-1930, 10p
Abstrakt: 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 phospho-diesterase (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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index