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| The EMBO Journal
(2001) 20, 1921–1930, doi:10.1093/emboj/20.8.1921 |
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| mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module |
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| Kimberly L. Dodge1, Samone Khouangsathiene1, Michael S. Kapiloff2, Robert Mouton1, Elaine V. Hill3, Miles D. Houslay3, Lorene K. Langeberg1 and John D. Scott1 |
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1 Howard Hughes Medical Institute and Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA 2 Department of Pediatrics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA 3 Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK To whom correspondence should be addressed John D. Scott, scott@ohsu.edu Received 16 January 2001; Revised 27 February 2001; Accepted 28 February 2001. |
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| Abstract |
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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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| Keywords: AKAP, cAMP, phosphodiesterase, PKA, signal transduction |
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