Open AccessLocal protein kinase A action proceeds through intact holoenzymes
Author(s) -
F. Donelson Smith,
Jessica L. Esseltine,
Patrick J. Nygren,
David Veesler,
Dominic P. Byrne,
Matthias Vonderach,
Ilya Strashnov,
Claire E. Eyers,
Patrick A. Eyers,
Lorene K. Langeberg,
John D. Scott
Publication year - 2017
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.aaj1669
Subject(s) - protein kinase a , protein subunit , microbiology and biotechnology , enzyme , kinase , chemistry , adenosine , biochemistry , enzyme activator , receptor , cyclic adenosine monophosphate , phosphorylation , biology , gene
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 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.
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