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A-kinase anchoring proteins: temporal and spatial regulation of intracellular signal transduction in the cardiovascular system.

The prototypical intracellular second messenger cAMP is locally controlled by multimolecular protein complexes organized by A-kinase anchoring proteins (AKAPs). AKAPs serve as scaffolds for different sets of cAMP-metabolizing enzymes that control cAMP gradients and regulate cellular responses. In addition to adenylyl cyclases and phosphodiesterases, AKAPs bind signaling enzymes and ion channels that are important regulators of cardiac contractility and pathophysiological myocyte remodeling and hypertrophy. Compartmentation increases the local concentration of cAMP signaling components, providing faster, higher fidelity regulation of cellular processes. This review series highlights the contribution of AKAPs in the heart as scaffold proteins integrating protein kinases, phosphatases and other effector molecules involved in cAMP-dependent signaling.