TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae

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Yerlikaya, Seda
Meusburger, Madeleine
Kumari, Romika
Huber, Alexandre
Anrather, Dorothea
Costanzo, Michael
Boone, Charles
Ammerer, Gustav
Baranov, Pavel V.
Loewith, Robbie
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Nutrient-sensitive phosphorylation of the S6 protein of the 40S subunit of the eukaryote ribosome is highly conserved. However, despite four decades of research, the functional consequences of this modification remain unknown. Revisiting this enigma in Saccharomyces cerevisiae, we found that the regulation of Rps6 phosphorylation on Ser-232 and Ser-233 is mediated by both TOR complex 1 (TORC1) and TORC2. TORC1 regulates phosphorylation of both sites via the poorly characterized AGC-family kinase Ypk3 and the PP1 phosphatase Glc7, whereas TORC2 regulates phosphorylation of only the N-terminal phosphosite via Ypk1. Cells expressing a nonphosphorylatable variant of Rps6 display a reduced growth rate and a 40S biogenesis defect, but these phenotypes are not observed in cells in which Rps6 kinase activity is compromised. Furthermore, using polysome profiling and ribosome profiling, we failed to uncover a role of Rps6 phosphorylation in either global translation or translation of individual mRNAs. Taking the results together, this work depicts the signaling cascades orchestrating Rps6 phosphorylation in budding yeast, challenges the notion that Rps6 phosphorylation plays a role in translation, and demonstrates that observations made with Rps6 knock-ins must be interpreted cautiously.
TORC1 , TORC2 , Ribsomal protein , S6 , Phosphorylation , Saccharomyces cerevisiae
Yerlikaya, S., Meusburger, M., Kumari, R., Huber, A., Anrather, D., Costanzo, M., Boone, C., Ammerer, G., Baranov, P. V. and Loewith, R. (2016) 'TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae', Molecular Biology of the Cell, 27(2), pp. 397-409. doi: 10.1091/mbc.E15-08-0594
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