NDLI: β-Adrenergic regulation requires direct anchoring of PKA to cardiac $Ca_{V}1.2$ channels via a leucine zipper interaction with A kinase-anchoring protein 15

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β-Adrenergic regulation requires direct anchoring of PKA to cardiac $Ca_{V}1.2$ channels via a leucine zipper interaction with A kinase-anchoring protein 15

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β-Adrenergic regulation requires direct anchoring of PKA to cardiac $Ca_{V}1.2$ channels via a leucine zipper interaction with A kinase-anchoring protein 15

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Scheuer, Todd Hulme, Joanne T. Westenbroek, Ruth E. Catterall, William A. Lin, Teddy W-c
Description	Author Affiliation: Hulme JT ( Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.);
Abstract	Activation of beta-adrenergic receptors and consequent phosphorylation by cAMP-dependent protein kinase A (PKA) greatly increases the L-type Ca2+ current through CaV1.2 channels in isolated cardiac myocytes. A kinase-anchoring protein 15 (AKAP15) coimmunoprecipitates with CaV1.2 channels isolated from rat heart membrane extracts and transfected cells, and it colocalizes with CaV1.2 channels and PKA in the transverse tubules of isolated ventricular myocytes. Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif. Disruption of PKA anchoring to CaV1.2 channels via AKAP15 using competing peptides markedly inhibits the beta-adrenergic regulation of CaV1.2 channels via the PKA pathway in ventricular myocytes. These results identify a conserved leucine zipper motif in the C terminus of the CaV1 family of Ca2+ channels that directly anchors an AKAP15-PKA signaling complex to ensure rapid and efficient regulation of L-type Ca2+ currents in response to beta-adrenergic stimulation and local increases in cAMP.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	22
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Calcium Channels, L-Type Metabolism Carrier Proteins Cyclic AMP-Dependent Protein Kinases Heart Physiology Membrane Proteins Receptors, Adrenergic, Beta A Kinase Anchor Proteins Amino Acid Sequence Animals Binding Sites Chemistry Leucine Zippers Molecular Sequence Data Muscle, Skeletal Rabbits Rats, Wistar Sequence Alignment Sequence Homology, Amino Acid Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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