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

Article Article scientifique Article Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9 eng 2020 author Plank Michaël 857393 author Perepelkina Mariya 730195 author Muller Markus Johann 125264 author Vaga Stefania author Zou Xiaoming 908955 author Bourgoint Clelia 795211 author Berti Marina 23206 author Saarbach Jacques 827625 author Haesendonckx Steven 765270 author Winssinger Nicolas 769664 author Aebersold Ruedi author Loewith Robbie Joséph 630703 655-671 10.1074/mcp.RA120.001955 1535-9476 http://www.mcponline.org/lookup/doi/10.1074/mcp.RA120.001955 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. Dewey 540 Dewey 570 Swiss National Science Foundation SystemsX program (#51RTP0_151037) CH 36 Département de chimie organique 141 43 Département de biologie moléculaire 161 false 814 Groupe Loewith 762 Groupe Winssinger Molecular and Cellular Proteomics 19 4 4c50fe8d-7d9b-47d6-a5b8-5988c71cab1c Article (Published version) Public 655.full.pdf 6881457 application/pdf CC BY openAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9	Molecular and Cellular Proteomics			2020	482	274

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Haesendonckx, Steven