A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress
| Autor: | Consuelo Montesinos, José Ramón Murguía, Silvia Lorenz, Guillem Hueso, Rafael Aparicio-Sanchis, Ramón Serrano |
|---|---|
| Přispěvatelé: | Serrano, Ramón |
| Rok vydání: | 2011 |
| Předmět: |
Amino
Ph homeostasis Saccharomyces cerevisiae Proteins Cerevisiae Intracellular pH Mutant Amino acid transport homoeostasis Saccharomyces cerevisiae Biology Signal transduction Protein Serine-Threonine Kinases Biochemistry Amino Acyl-tRNA Synthetases Saccharomyces RNA Transfer Leucine Stress Physiological Eukaryotic initiation factor Gene Expression Regulation Fungal Acid BIOQUIMICA Y BIOLOGIA MOLECULAR Homeostasis Amino Acids Protein kinase A Molecular Biology Acetic Acid chemistry.chemical_classification pH Leucine transport RNA Fungal Cell Biology Hydrogen-Ion Concentration transduction Adaptation Physiological Amino acid chemistry transport Mutation Gcn2 signal Intracellular Plasmids |
| Zdroj: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia instname Digital.CSIC. Repositorio Institucional del CSIC |
| ISSN: | 1470-8728 |
| Popis: | Intracellular pH conditions many cellular systems, but its mechanisms of regulation and perception are mostly unknown. We have identified two yeast genes important for tolerance to intracellular acidification caused by weak permeable acids. One corresponded to LEU2 and functions by removing the dependency of the leu2 mutant host strain on uptake of extracellular leucine. Leucine transport is inhibited by intracellular acidification, and either leucine oversupplementation or overexpression of the transporter gene BAP2 improved acid growth. Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation. Gcn2 phosphorylates eIF2α (eukaryotic initiation factor 2α) (Sui2) at Ser51 and this inhibits general translation, but activates that of Gcn4, a transcription factor for amino acid biosynthetic genes. Intracellular acidification activates Gcn2 probably by inhibition of aminoacyl-tRNA synthetases because we observed accumulation of uncharged tRNAleu without leucine depletion. Gcn2 is required for leucine transport and a gcn2-null mutant is sensitive to acid stress if auxotrophic for leucine. Gcn4 is required for neither leucine transport nor acid tolerance, but a S51A sui2 mutant is acid-sensitive. This suggests that Gcn2, by phosphorylating eIF2α, may activate translation of an unknown regulator of amino acid transporters different from Gcn4. This work was funded by grants from the Spanish Ministerio de Ciencia e Innovacion (Madrid) [grant number BFU2008-00604] and the Generalitat Valenciana (Valencia) [grantnumber Prometeo/2010/038]. |
| Databáze: | OpenAIRE |
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