Distinct enzyme combinations in AKAP signalling complexes permit functional diversity

Nat Cell Biol. 2005 Nov;7(11):1066-73. doi: 10.1038/ncb1315.


Specificity in cell signalling can be influenced by the targeting of different enzyme combinations to substrates. The A-kinase anchoring protein AKAP79/150 is a multivalent scaffolding protein that coordinates the subcellular localization of second-messenger-regulated enzymes, such as protein kinase A, protein kinase C and protein phosphatase 2B. We developed a new strategy that combines RNA interference of the endogenous protein with a protocol that selects cells that have been rescued with AKAP79/150 forms that are unable to anchor selected enzymes. Using this approach, we show that AKAP79/150 coordinates different enzyme combinations to modulate the activity of two distinct neuronal ion channels: AMPA-type glutamate receptors and M-type potassium channels. Utilization of distinct enzyme combinations in this manner provides a means to expand the repertoire of cellular events that the same AKAP modulates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology*
  • Calcineurin / metabolism*
  • Calcineurin / physiology
  • Calcineurin Inhibitors
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Discs Large Homolog 1 Protein
  • Humans
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / metabolism
  • Membrane Transport Proteins / physiology*
  • Models, Biological
  • Muscarinic Agonists
  • Potassium Channels / metabolism
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism


  • Adaptor Proteins, Signal Transducing
  • Calcineurin Inhibitors
  • Carrier Proteins
  • DLG1 protein, human
  • Discs Large Homolog 1 Protein
  • Membrane Proteins
  • Membrane Transport Proteins
  • Muscarinic Agonists
  • Potassium Channels
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin