Local protein kinase A action proceeds through intact holoenzymes


Smith, FD, Esseltine, JL, Nygren, PJ, Veesler, D, Byrne, DP, Vonderach, M, Strashnov, I, Eyers, CE ORCID: 0000-0002-3223-5926, Eyers, PA ORCID: 0000-0002-9220-2966, Langeberg, LK et al (show 1 more authors) (2017) Local protein kinase A action proceeds through intact holoenzymes. Science, 356 (6344). pp. 1288-1293.

[img] Text
Smth et al 2-16-17 FInal combined.pdf - Author Accepted Manuscript
Download (7MB)

Abstract

Hormones can transmit signals through adenosine 3’,5’-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 (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 sub-assemblies within 150 to 250Å 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. In contrast, little, if any PKA activity was detected in the nucleus. Hence the parameters of anchored PKA holoenzyme action are much more restricted than originally anticipated.

Item Type: Article
Uncontrolled Keywords: Cell Line, Tumor, Mitochondria, Animals, Humans, Mice, Holoenzymes, Cyclic AMP-Dependent Protein Kinases, Recombinant Fusion Proteins, Cyclic AMP, Microscopy, Electron, Signal Transduction, Protein Binding, Phosphorylation, A Kinase Anchor Proteins, Protein Stability
Depositing User: Symplectic Admin
Date Deposited: 12 Jun 2017 06:55
Last Modified: 19 Jan 2023 07:03
DOI: 10.1126/science.aaj1669
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3007902
Dimensions
Altmetric
CORE (COnnecting REpositories)