title: State transitions in the TORC1 signaling pathway and information processing in Saccharomyces cerevisiae.
abstract: TOR kinase complex I (TORC1) is a key regulator of cell growth and metabolism in all eukaryotes. Previous studies in yeast have shown that three GTPases-Gtr1, Gtr2, and Rho1-bind to TORC1 in nitrogen and amino acid starvation conditions to block phosphorylation of the S6 kinase Sch9 and activate protein phosphatase 2A (PP2A). This leads to downregulation of 450 Sch9-dependent protein and ribosome synthesis genes and upregulation of 100 PP2A-dependent nitrogen assimilation and amino acid synthesis genes. Here, using bandshift assays and microarray measurements, we show that the TORC1 pathway also populates three other stress/starvation states. First, in glucose starvation conditions, the AMP-activated protein kinase (AMPK/Snf1) and at least one other factor push the TORC1 pathway into an off state, in which Sch9-branch signaling and PP2A-branch signaling are both inhibited. Remarkably, the TORC1 pathway remains in the glucose starvation (PP2A inhibited) state even when cells are simultaneously starved for nitrogen and glucose. Second, in osmotic stress, the MAPK Hog1/p38 drives the TORC1 pathway into a different state, in which Sch9 signaling and PP2A-branch signaling are inhibited, but PP2A-branch signaling can still be activated by nitrogen starvation. Third, in oxidative stress and heat stress, TORC1-Sch9 signaling is blocked while weak PP2A-branch signaling occurs. Together, our data show that the TORC1 pathway acts as an information-processing hub, activating different genes in different conditions to ensure that available energy is allocated to drive growth, amino acid synthesis, or a stress response, depending on the needs of the cell.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721-0206.
authors.forename: James E
authors.initials: JE
authors.lastname: Hughes Hallett
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721-0206.
authors.forename: Xiangxia
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721-0206 capaldi@email.arizona.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Capaldi
mesh_terms: D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D059467:Transcriptome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae; D054648:Protein Phosphatase 2
keywords: PP2A; Snf1; TORC1
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