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). 1288 - 1293.

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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
Depositing User: Symplectic Admin
Date Deposited: 12 Jun 2017 06:55
Last Modified: 01 Sep 2022 16:10
DOI: 10.1126/science.aaj1669
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3007902