AKAP signaling complexes: getting to the heart of the matter.
Subcellular compartmentalization of protein kinases and phosphatases through their interaction with A-kinase anchoring proteins (AKAPs) provides a mechanism to control signal transduction events at specific sites within the cell. Recent findings suggest that these anchoring proteins dynamically assemble different cAMP effectors to control the cellular actions of cAMP spatially and temporally. In the heart, signaling events such as the onset of cardiac hypertrophy are influenced by muscle-specific mAKAP signaling complexes that target protein kinase A (PKA), the cAMP-responsive guanine-nucleotide exchange factor EPAC and cAMP-selective phosphodiesterase 4 (PDE4). Mediation of signaling events by AKAPs might also have a role in the control of lipolysis in adipocytes, where insulin treatment reduces the association of AKAPs with G-protein-coupled receptors. These are only two examples of how AKAPs contribute to specificity in cAMP signaling. This review will explore recent development that illustrates the role of multiprotein complexes in the regulation of cAMP signaling.
McConnachie
George
G
Howard Hughes Medical Institute, Vollum Institute, L-474, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
Langeberg
Lorene K
LK
Scott
John D
JD
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4