Function to Failure: Compartmentalization of Cardiomyocyte Signaling by A-Kinase-Anchoring Proteins
Compartmentalization of signaling enzymes allows cardiomyocytes to make contextually specific decisions using a common set of second messengers. Though first identified by their role in localizing the pleiotropic cAMP-dependent protein kinase A (PKA) to specific intracellular organelles and compartments, A-kinase-anchoring proteins (AKAPs) are a structurally and functionally diverse family of multivalent scaffolds that organize “signalosomes” constituting critical nodes in the cell-type-specific network of intracellular signaling pathways. This chapter summarizes the role of AKAPs in cardiomyocytes, with a focus on the intersection of compartmentalized signaling and cardiac pathophysiology.
Compliance with Ethical Standards
This work was funded by the State of Connecticut Department of Public Health Grant 2014-0133 (K.D.K.) and the US National Institutes of Health Grants HL126825 (K.D.K. and M.S.K.) and HL075398 (M.S.K.)
Conflict of Interest Statement
Drs. Kapiloff and Dodge-Kafka are coinventors of patented intellectual property concerning the use of RSK3 and AKAP6 inhibitors for the treatment of heart failure and by which they and the University of Miami may gain royalties from future commercialization. Dr. Kapiloff is the manager of Anchored RSK3 Inhibitors, LLC, and president of Cardiac RSK3 Inhibitors, LLC, companies interested in developing RSK3-targeted therapies and in which Dr. Kapiloff holds equity.
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