Abstract
Rapid, voltage-dependent potentiation of skeletal muscle L-type calcium channels requires phosphorylation by cAMP-dependent protein kinase (PKA) anchored via an A kinase anchoring protein (AKAP). Here we report the isolation, primary sequence determination, and functional characterization of AKAP15, a lipid-anchored protein of 81 amino acid residues with a single amphipathic helix that binds PKA. AKAP15 colocalizes with L-type calcium channels in transverse tubules and is associated with L-type calcium channels in transfected cells. A peptide fragment of AKAP15 encompassing the RII-binding domain blocks voltage-dependent potentiation. These results indicate that AKAP15 targets PKA to the calcium channel and plays a critical role in voltage-dependent potentiation and regulation of skeletal muscle contraction. The expression of AKAP15 in the brain and heart suggests that it may mediate rapid PKA regulation of L-type calcium channels in neurons and cardiac myocytes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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A Kinase Anchor Proteins
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Acetylation
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Blotting, Northern
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Calcium Channels / analysis
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Calcium Channels / metabolism*
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Calcium Channels, L-Type
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Carrier Proteins / analysis
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cell Line
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Consensus Sequence
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Gene Expression Regulation, Enzymologic / physiology
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Humans
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Ion Channel Gating / physiology
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Kidney / cytology
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Membrane Proteins / analysis
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Microsomes / chemistry
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Microsomes / enzymology
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Molecular Sequence Data
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Muscle Contraction / physiology
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Muscle Proteins / analysis
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Muscle Proteins / metabolism
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Muscle, Skeletal / chemistry*
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Muscle, Skeletal / enzymology
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Mutagenesis / physiology
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Precipitin Tests
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Protein Binding / physiology
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RNA, Messenger / analysis
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Rabbits
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Rats
Substances
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A Kinase Anchor Proteins
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AKAP7 protein, human
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Adaptor Proteins, Signal Transducing
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Calcium Channels
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Calcium Channels, L-Type
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Carrier Proteins
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Membrane Proteins
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Muscle Proteins
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RNA, Messenger
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Cyclic AMP-Dependent Protein Kinases