Review
A-kinase anchoring proteins: Molecular regulators of the cardiac stress response

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Abstract

In response to stress or injury the heart undergoes a pathological remodeling process, associated with hypertrophy, cardiomyocyte death and fibrosis, that ultimately causes cardiac dysfunction and heart failure. It has become increasingly clear that signaling events associated with these pathological cardiac remodeling events are regulated by scaffolding and anchoring proteins, which allow coordination of pathological signals in space and time. A-kinase anchoring proteins (AKAPs) constitute a family of functionally related proteins that organize multiprotein signaling complexes that tether the cAMP-dependent protein kinase (PKA) as well as other signaling enzymes to ensure integration and processing of multiple signaling pathways. This review will discuss the role of AKAPs in the cardiac response to stress. Particular emphasis will be given to the adaptative process associated with cardiac hypoxia as well as the remodeling events linked to cardiac hypertrophy and heart failure. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Highlights

► A-kinase anchoring proteins (AKAPs) assemble multienzyme signaling complexes in cells. ► AKAPs coordinate signaling cascades that regulate the cardiac response to stress. ► We analyze recent literature describing the role of AKAPs in cardiac pathophysiology. ► We discuss the role of AKAPs in the hypoxic heart and in cardiac remodeling.

Keywords

A kinase anchoring protein (AKAP)
Protein kinase A
Cardiac remodeling
Signaling
Cardiomyocyte

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This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.