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A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1

Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein–protein interactome for yeast PA...

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Autores principales: DeMille, Desiree, Bikman, Benjamin T., Mathis, Andrew D., Prince, John T., Mackay, Jordan T., Sowa, Steven W., Hall, Tacie D., Grose, Julianne H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091833/
https://www.ncbi.nlm.nih.gov/pubmed/24850888
http://dx.doi.org/10.1091/mbc.E13-10-0631
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author DeMille, Desiree
Bikman, Benjamin T.
Mathis, Andrew D.
Prince, John T.
Mackay, Jordan T.
Sowa, Steven W.
Hall, Tacie D.
Grose, Julianne H.
author_facet DeMille, Desiree
Bikman, Benjamin T.
Mathis, Andrew D.
Prince, John T.
Mackay, Jordan T.
Sowa, Steven W.
Hall, Tacie D.
Grose, Julianne H.
author_sort DeMille, Desiree
collection PubMed
description Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein–protein interactome for yeast PAS kinase 1 (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1 binding partners expand the role of PAS kinase in glucose homeostasis, including new pathways involved in mitochondrial metabolism. In addition, the interactome suggests novel roles for PAS kinase in cell growth (gene/protein expression, replication/cell division, and protein modification and degradation), vacuole function, and stress tolerance. In vitro kinase studies using a subset of 25 of these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates. Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212 and for the subsequent inhibition of respiration. This respiratory role of PAS kinase is consistent with the reported hypermetabolism of PAS kinase–deficient mice, identifying a possible molecular mechanism and solidifying the evolutionary importance of PAS kinase in the regulation of glucose homeostasis.
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spelling pubmed-40918332014-10-01 A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1 DeMille, Desiree Bikman, Benjamin T. Mathis, Andrew D. Prince, John T. Mackay, Jordan T. Sowa, Steven W. Hall, Tacie D. Grose, Julianne H. Mol Biol Cell Articles Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein–protein interactome for yeast PAS kinase 1 (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1 binding partners expand the role of PAS kinase in glucose homeostasis, including new pathways involved in mitochondrial metabolism. In addition, the interactome suggests novel roles for PAS kinase in cell growth (gene/protein expression, replication/cell division, and protein modification and degradation), vacuole function, and stress tolerance. In vitro kinase studies using a subset of 25 of these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates. Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212 and for the subsequent inhibition of respiration. This respiratory role of PAS kinase is consistent with the reported hypermetabolism of PAS kinase–deficient mice, identifying a possible molecular mechanism and solidifying the evolutionary importance of PAS kinase in the regulation of glucose homeostasis. The American Society for Cell Biology 2014-07-15 /pmc/articles/PMC4091833/ /pubmed/24850888 http://dx.doi.org/10.1091/mbc.E13-10-0631 Text en © 2014 DeMille et al. 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). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
DeMille, Desiree
Bikman, Benjamin T.
Mathis, Andrew D.
Prince, John T.
Mackay, Jordan T.
Sowa, Steven W.
Hall, Tacie D.
Grose, Julianne H.
A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1
title A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1
title_full A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1
title_fullStr A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1
title_full_unstemmed A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1
title_short A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1
title_sort comprehensive protein–protein interactome for yeast pas kinase 1 reveals direct inhibition of respiration through the phosphorylation of cbf1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091833/
https://www.ncbi.nlm.nih.gov/pubmed/24850888
http://dx.doi.org/10.1091/mbc.E13-10-0631
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