Contributions of protein kinase A anchoring proteins to compartmentation of cAMP signaling in the heart.
The cAMP-dependent protein kinase (PKA) transduces signals in the heart initiated by beta(1)-adrenergic, G-protein-coupled receptors after norepinephrine, sympathetic stimulation. Signaling through this pathway results in a characteristic set of cellular responses, including increases in ion fluxes and contractile strength, mobilization of energy stores, and changes in gene expression. Not all receptors that activate adenylate cyclase and increase cAMP levels, however, cause the cardiac myocyte to react in this manner. Research in the field of signal transduction over the last 25 years has addressed this issue of specificity in signaling by diffusable second messengers. PKA is in part targeted to discrete cellular locations by A-kinase anchoring proteins. Through anchoring and formation of multienzyme complexes, specific, localized signal transduction is possible. I discuss in this review recent advances in the understanding of PKA signaling complexes in the cardiac myocyte.
Department of Pediatrics, Heart Research Center, Oregon Health and Science University, Portland, Oregon 97201, USA. kapiloff@ohsu.edu
Michael S
MS
Kapiloff
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D008133:Long QT Syndrome / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D054758:A Kinase Anchor Proteins; C112596:AKAP7 protein, human; C119719:AKAP9 protein, human; D048868:Adaptor Proteins, Signal Transducing; D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D017868:Cyclic AMP-Dependent Protein Kinases