Primary structure and function of an A kinase anchoring protein associated with calcium channels

Neuron. 1998 May;20(5):1017-26. doi: 10.1016/s0896-6273(00)80482-1.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • A Kinase Anchor Proteins
  • Acetylation
  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Calcium Channels / analysis
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line
  • Consensus Sequence
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Gene Expression Regulation, Enzymologic / physiology
  • Humans
  • Ion Channel Gating / physiology
  • Kidney / cytology
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Microsomes / chemistry
  • Microsomes / enzymology
  • Molecular Sequence Data
  • Muscle Contraction / physiology
  • Muscle Proteins / analysis
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / enzymology
  • Mutagenesis / physiology
  • Precipitin Tests
  • Protein Binding / physiology
  • RNA, Messenger / analysis
  • Rabbits
  • Rats


  • A Kinase Anchor Proteins
  • AKAP7 protein, human
  • Adaptor Proteins, Signal Transducing
  • Calcium Channels
  • Calcium Channels, L-Type
  • Carrier Proteins
  • Membrane Proteins
  • Muscle Proteins
  • RNA, Messenger
  • Cyclic AMP-Dependent Protein Kinases