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The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates

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 th...

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Autores principales: Soulard, Alexandre, Cremonesi, Alessio, Moes, Suzette, Schütz, Frédéric, Jenö, Paul, Hall, Michael N.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947482/
https://www.ncbi.nlm.nih.gov/pubmed/20702584
http://dx.doi.org/10.1091/mbc.E10-03-0182
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author Soulard, Alexandre
Cremonesi, Alessio
Moes, Suzette
Schütz, Frédéric
Jenö, Paul
Hall, Michael N.
author_facet Soulard, Alexandre
Cremonesi, Alessio
Moes, Suzette
Schütz, Frédéric
Jenö, Paul
Hall, Michael N.
author_sort Soulard, Alexandre
collection PubMed
description 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.
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spelling pubmed-29474822010-12-16 The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates Soulard, Alexandre Cremonesi, Alessio Moes, Suzette Schütz, Frédéric Jenö, Paul Hall, Michael N. Mol Biol Cell Articles 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. The American Society for Cell Biology 2010-10-01 /pmc/articles/PMC2947482/ /pubmed/20702584 http://dx.doi.org/10.1091/mbc.E10-03-0182 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution-Noncommercial-Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Soulard, Alexandre
Cremonesi, Alessio
Moes, Suzette
Schütz, Frédéric
Jenö, Paul
Hall, Michael N.
The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates
title The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates
title_full The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates
title_fullStr The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates
title_full_unstemmed The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates
title_short The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates
title_sort rapamycin-sensitive phosphoproteome reveals that tor controls protein kinase a toward some but not all substrates
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947482/
https://www.ncbi.nlm.nih.gov/pubmed/20702584
http://dx.doi.org/10.1091/mbc.E10-03-0182
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