A-kinase anchoring protein targeting of protein kinase A in the heart.

There is increasing evidence that subcellular targeting of signaling molecules is an important means of regulating the protein kinase A (PKA) pathway. Subcellular organization of the signaling molecules in the PKA pathway insures that a signal initiated at the receptor level is transferred efficiently to a PKA substrate eliciting some cellular response. This subcellular targeting appears to regulate the function of a highly specialized cell such as the cardiac myocyte. This review focuses on A-kinase anchoring proteins (AKAPs) which are expressed in the heart. It has been determined that, of the approximately 13 different AKAPs expressed in cardiac tissue, several of these are expressed in cardiac myocytes. These AKAPs bind several PKA substrates and some appear to regulate PKA-dependent phosphorylation of these substrates. AKAP tethering of PKA may be essential for efficient regulation of cardiac muscle contraction. The ability of an AKAP to anchor PKA may be altered in the failing heart, thus compromising the ability of the myocyte to respond to stimuli which elicit the PKA pathway.