Primary structure and function of an A kinase anchoring protein associated with calcium channels.
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.
Gray
P C
PC
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Johnson
B D
BD
Westenbroek
R E
RE
Hays
L G
LG
Yates
J R
JR
Scheuer
T
T
Catterall
W A
WA
Murphy
B J
BJ
D054758:A Kinase Anchor Proteins; D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015220:Calcium Channels / Q000032:analysis / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D016384:Consensus Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008861:Microsomes / Q000737:chemistry / Q000201:enzymology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000201:enzymology; D016296:Mutagenesis / Q000502:physiology; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats
D054758:A Kinase Anchor Proteins; C112596:AKAP7 protein, human; D048868:Adaptor Proteins, Signal Transducing; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases