title: mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module.
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.
authors: Howard Hughes Medical Institute and Vollum Institute, and Department of Pediatrics, Oregon Health Sciences University, Portland, OR 97201-3098, USA.
authors: K L
authors: KL
authors: Dodge
authors: S
authors: S
authors: Khouangsathiene
authors: M S
authors: MS
authors: Kapiloff
authors: R
authors: R
authors: Mouton
authors: E V
authors: EV
authors: Hill
authors: M D
authors: MD
authors: Houslay
authors: L K
authors: LK
authors: Langeberg
authors: J D
authors: JD
authors: Scott
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005246:Feedback; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction
chemical_list: D009124:Muscle Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4