doi: 10.1161/01.RES.0000218273.91741.30
© 2006 American Heart Association, Inc.
Reviews |
Compartmentation of Cyclic Nucleotide Signaling in the Heart
The Role of A-Kinase Anchoring Proteins
From the Pat and Jim Calhoun Center for Cardiology (K.L.D.-K.), University of Connecticut Health Center, Farmington; and Howard Hughes Medical Institute (L.L., J.D.S.), Vollum Institute, Oregon Health and Sciences University, Portland.
Correspondence to Kimberly L. Dodge-Kafka, Pat and Jim Calhoun Center for Cardiology (K.L.D.-K.), University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030. E-mail dodge{at}uchc.edu
This Review is part of a thematic series on Microdomains in Cardiovascular Signaling, which includes the following articles:
Caveolae and Caveolins in the Cardiovascular System
Focal Adhesion: Paradigm for a Signaling Nexus
Vesicular Trafficking of Tyrosine Kinase Receptors and Associated Proteins in the Regulation of Signaling and Vascular Function
Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of A-Kinase Anchoring Proteins
Targeting Cyclic Nucleotide Signaling
G Protein–Coupled Receptor Trafficking
Kathy K. Griendling and David A. Kass Editors
The activation of the cyclic nucleotide protein kinase A (PKA) and PKG by their respective second messengers is responsible for the modulation of many cellular functions in the heart including cardiac hypertrophy, strength of contraction, and ion flux. However, several studies have revealed that a general increase in cyclic nucleotide concentration in the cell is not sufficient for the specific regulation of target proteins. These studies found that PKA and PKG must be colocalized with their targets to ensure spatial–temporal control of substrate phosphorylation. This compartmentation of cyclic nucleotide signaling is accomplished by tethering the protein kinases with their respective substrates through the association with scaffolding proteins. For cAMP signaling, A-kinase anchoring proteins (AKAPs) provide a molecular mechanism for cAMP compartmentation, allowing for the precise control of PKA-mediated phosphorylation events. (cAMP, PKA, AKAP, PKG).
Key Words: cGMP • ion channels • protein kinase A phosphorylation • signal transduction • signaling pathways
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