TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in<i>Saccharomyces cerevisiae</i>

Yerlikaya, Seda; Meusburger, Madeleine; Kumari, Romika; Huber, Alexandre; Anrather, Dorothea; Costanzo, Michael; Boone, Charles; Ammerer, Gustav; Baranov, Pavel V.; Loewith, Robbie

doi:10.1091/mbc.e15-08-0594

Cited by 80 publications

(86 citation statements)

References 54 publications

(74 reference statements)

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“…Instead cell growth and size as well as ribosome biogenesis were affected (Ruvinsky et al, 2005; Chauvin et al, 2014). The same result was observed in yeast expressing non-phoshorylatable RPS6 (Yerlikaya et al, 2016). However, phosphorylation of the C-terminal Ser residues of RPS6 has been used as a robust and recognized readout for TOR activity in animals and yeast (Meyuhas, 2008, 2015; Yerlikaya et al, 2016).…”

Section: Discussionsupporting

confidence: 78%

“…The same result was observed in yeast expressing non-phoshorylatable RPS6 (Yerlikaya et al, 2016). However, phosphorylation of the C-terminal Ser residues of RPS6 has been used as a robust and recognized readout for TOR activity in animals and yeast (Meyuhas, 2008, 2015; Yerlikaya et al, 2016). In this study, a decrease in RPS6 phosphorylation in response to TOR inactivation was observed ( Figures 5 and 7 ).…”

Section: Discussionsupporting

confidence: 78%

“…The X!Tandem analysis predicted a phosphorylation site on Ser240 (SRLpSSAPAKPVAA: Figure 5 ; Supplementary Figure S3). This serine seems to be conserved in the eukaryotic RPS6 proteins, including plants, and was previously identified as being phosphorylated following TOR activation in yeast and animals (Pende, 2006; Meyuhas, 2008; Yerlikaya et al, 2016) ( Figure 6 ). In order to clarify the actual position of the phosphorylated residue in this peptide, the phosphoproteomic results were submitted to a Phoscalc statistical analysis (MacLean et al, 2008).…”

Section: Resultsmentioning

confidence: 84%

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The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S6

et al. 2016

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Protein translation is an energy consuming process that has to be fine-tuned at both the cell and organism levels to match the availability of resources. The target of rapamycin kinase (TOR) is a key regulator of a large range of biological processes in response to environmental cues. In this study, we have investigated the effects of TOR inactivation on the expression and regulation of Arabidopsis ribosomal proteins at different levels of analysis, namely from transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated down-regulation of the transcription and translation of nuclear-encoded mRNAs coding for plastidic ribosomal proteins, which could explain the chlorotic phenotype of the TOR silenced plants. We have identified in the 5′ untranslated regions (UTRs) of this set of genes a conserved sequence related to the 5′ terminal oligopyrimidine motif, which is known to confer translational regulation by the TOR kinase in other eukaryotes. Furthermore, the phosphoproteomic analysis of the ribosomal fraction following TOR inactivation revealed a lower phosphorylation of the conserved Ser240 residue in the C-terminal region of the 40S ribosomal protein S6 (RPS6). These results were confirmed by Western blot analysis using an antibody that specifically recognizes phosphorylated Ser240 in RPS6. Finally, this antibody was used to follow TOR activity in plants. Our results thus uncover a multi-level regulation of plant ribosomal genes and proteins by the TOR kinase.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 84%

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The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S6

et al. 2016

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“…Thus, Rps6 phosphorylation mediated by TORC1 (Psk1) and TORC2 (Gad8) is not biologically relevant during the stress response in this organism. Recent global polysome and ribosome profiling studies in budding yeast have also failed to uncover a role of Rps6 phosphorylation in global or individual mRNAs translation46.…”

Section: Discussionmentioning

confidence: 99%

Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast

Madrid

Vázquez-Marín

Franco

et al. 2016

Sci Rep

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In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms. The first one involves TORC2 and its downstream effector, Akt ortholog Gad8, which together with TORC1 target Psk1 increase protein levels of the PKC ortholog Pck2 during cell wall stress or glucose starvation. Also, Ryh1 activates Pmk1 in a TORC2-independent fashion by prompting plasma membrane trafficking and stabilization of upstream activators of the MAPK cascade, including PDK ortholog Ksg1 or Rho1 GEF Rgf1. Besides, stress-activated Pmk1 cross-inhibits Ryh1 signaling by decreasing the GTPase activation cycle, and this ensures cell growth during alterations in phosphoinositide metabolism. Our results reveal a highly intricate cross-regulatory relationship between both pathways that warrants adequate cell adaptation and survival in response to environmental changes.

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“…The results are in agreement with those reported previously. In yeast, Ser and Thr residues around the conserved phosphorylation sites appear to function redundantly . In the ypk3Δ cells, human S6Ks showed much lower activity than that of OsS6KΔ107 (Fig.…”

Section: Discussionmentioning

confidence: 98%

The activation mechanism of plant S6 kinase (S6K), a substrate of TOR kinase, is different from that of mammalian S6K

2019

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The S6 kinases (S6Ks) are known to be activated by the target of rapamycin through phosphorylation of their hydrophobic motif (HM). However, our previous research showed that the HM site of plant S6Ks is not phosphorylated and is not essential for their activity in yeast cells lacking Ypk3, an ortholog of mammalian S6K. Here, we demonstrate that the HM site of mammalian S6Ks is phosphorylated and is indispensable for their activity in yeast ypk3∆ cells. Furthermore, pseudo‐phosphorylation at the HM site of plant S6Ks results in regaining of activity that is lost due to mutation in the conserved phosphorylation sites, namely the T‐loop and Turn motif. These results indicate the activation mechanism of plant S6Ks is different from that of mammals.

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

Cited by 80 publications

References 54 publications

The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S6

The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S6

Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast

The activation mechanism of plant S6 kinase (S6K), a substrate of TOR kinase, is different from that of mammalian S6K

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