Local protein kinase A action proceeds through intact holoenzymes

Research output: Contribution to journalArticlepeer-review

  • Authors:
  • F Donelson Smith
  • Jessica L Esseltine
  • Patrick J Nygren
  • David Veesler
  • Dominic P Byrne
  • And 6 others
  • External authors:
  • Matthias Vonderach
  • Ilya Strashnov
  • Claire Eyers
  • Patrick A. Eyers
  • Lorene K Langeberg
  • John D. Scott


Hormones can transmit signals through adenosine 3ʹ,5ʹ-monophosphate (cAMP) to precise intracellular locations. The fidelity of these responses relies on the activation of localized protein kinase A (PKA) holoenzymes. Association of PKA regulatory type II (RII) subunits with A-kinase–anchoring proteins (AKAPs) confers location, and catalytic (C) subunits phosphorylate substrates. Single-particle electron microscopy demonstrated that AKAP79 constrains RII-C subassemblies within 150 to 250 angstroms of its targets. Native mass spectrometry established that these macromolecular assemblies incorporated stoichiometric amounts of cAMP. Chemical-biology– and live cell–imaging techniques revealed that catalytically active PKA holoenzymes remained intact within the cytoplasm. These findings indicate that the parameters of anchored PKA holoenzyme action are much more restricted than originally anticipated.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1288-1293
Number of pages6
Issue number6344
Early online date23 Jun 2017
Publication statusPublished - 2017