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Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9

Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of ex...

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Autores principales: Plank, Michael, Perepelkina, Mariya, Müller, Markus, Vaga, Stefania, Zou, Xiaoming, Bourgoint, Clélia, Berti, Marina, Saarbach, Jacques, Haesendonckx, Steven, Winssinger, Nicolas, Aebersold, Ruedi, Loewith, Robbie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124472/
https://www.ncbi.nlm.nih.gov/pubmed/32102971
http://dx.doi.org/10.1074/mcp.RA120.001955
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author Plank, Michael
Perepelkina, Mariya
Müller, Markus
Vaga, Stefania
Zou, Xiaoming
Bourgoint, Clélia
Berti, Marina
Saarbach, Jacques
Haesendonckx, Steven
Winssinger, Nicolas
Aebersold, Ruedi
Loewith, Robbie
author_facet Plank, Michael
Perepelkina, Mariya
Müller, Markus
Vaga, Stefania
Zou, Xiaoming
Bourgoint, Clélia
Berti, Marina
Saarbach, Jacques
Haesendonckx, Steven
Winssinger, Nicolas
Aebersold, Ruedi
Loewith, Robbie
author_sort Plank, Michael
collection PubMed
description Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases.
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spelling pubmed-71244722020-04-09 Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9 Plank, Michael Perepelkina, Mariya Müller, Markus Vaga, Stefania Zou, Xiaoming Bourgoint, Clélia Berti, Marina Saarbach, Jacques Haesendonckx, Steven Winssinger, Nicolas Aebersold, Ruedi Loewith, Robbie Mol Cell Proteomics Research Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases. The American Society for Biochemistry and Molecular Biology 2020-04 2020-02-26 /pmc/articles/PMC7124472/ /pubmed/32102971 http://dx.doi.org/10.1074/mcp.RA120.001955 Text en © 2020 Plank et al. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle Research
Plank, Michael
Perepelkina, Mariya
Müller, Markus
Vaga, Stefania
Zou, Xiaoming
Bourgoint, Clélia
Berti, Marina
Saarbach, Jacques
Haesendonckx, Steven
Winssinger, Nicolas
Aebersold, Ruedi
Loewith, Robbie
Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9
title Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9
title_full Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9
title_fullStr Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9
title_full_unstemmed Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9
title_short Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9
title_sort chemical genetics of agc-kinases reveals shared targets of ypk1, protein kinase a and sch9
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124472/
https://www.ncbi.nlm.nih.gov/pubmed/32102971
http://dx.doi.org/10.1074/mcp.RA120.001955
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