The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates.

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State: Public
Version: author
Serval ID
serval:BIB_0F9AEF8931C2
Type
Article: article from journal or magazin.
Collection
Publications
Title
The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates.
Journal
Molecular Biology of the Cell
Author(s)
Soulard A., Cremonesi A., Moes S., Schütz F., Jenö P., Hall M.N.
ISSN
1939-4586 (Electronic)
ISSN-L
1059-1524
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
21
Number
19
Pages
3475-3486
Language
english
Abstract
Regulation of cell growth requires extensive coordination of several processes including transcription, ribosome biogenesis, translation, nutrient metabolism, and autophagy. In yeast, the protein kinases Target of Rapamycin (TOR) and protein kinase A (PKA) regulate these processes and are thereby the main activators of cell growth in response to nutrients. How TOR, PKA, and their corresponding signaling pathways are coordinated to control the same cellular processes is not understood. Quantitative analysis of the rapamycin-sensitive phosphoproteome combined with targeted analysis of PKA substrates suggests that TOR complex 1 (TORC1) activates PKA but only toward a subset of substrates. Furthermore, we show that TORC1 signaling impinges on BCY1, the negative regulatory subunit of PKA. Inhibition of TORC1 with rapamycin leads to BCY1 phosphorylation on several sites including T129. Phosphorylation of BCY1 T129 results in BCY1 activation and inhibition of PKA. TORC1 inhibits BCY1 T129 phosphorylation by phosphorylating and activating the S6K homolog SCH9 that in turn inhibits the MAP kinase MPK1. MPK1 phosphorylates BCY1 T129 directly. Thus, TORC1 activates PKA toward some substrates by preventing MPK1-mediated activation of BCY1.

Keywords
Amino Acid Sequence, Cyclic AMP-Dependent Protein Kinases/metabolism, Enzyme Activation/drug effects, Isotope Labeling, Molecular Sequence Data, Phosphopeptides/chemistry, Phosphopeptides/metabolism, Phosphoproteins/metabolism, Phosphorylation/drug effects, Phosphothreonine/metabolism, Proteome/metabolism, Saccharomyces cerevisiae/drug effects, Saccharomyces cerevisiae/enzymology, Saccharomyces cerevisiae Proteins/antagonists & inhibitors, Saccharomyces cerevisiae Proteins/metabolism, Sirolimus/pharmacology, Substrate Specificity/drug effects, TOR Serine-Threonine Kinases/antagonists & inhibitors, TOR Serine-Threonine Kinases/metabolism, Transcription Factors/metabolism
Pubmed
Web of science
Create date
20/02/2017 18:04
Last modification date
20/08/2019 13:36
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