title: Reciprocal phosphorylation of yeast glycerol-3-phosphate dehydrogenases in adaptation to distinct types of stress.
abstract: Eukaryotic cells have evolved mechanisms for ensuring growth and survival in the face of stress caused by a fluctuating environment. Saccharomyces cerevisiae has two homologous glycerol-3-phosphate dehydrogenases, Gpd1 and Gpd2, that are required to endure various stresses, including hyperosmotic shock and hypoxia. These enzymes are only partially redundant, and their unique functions were attributed previously to differential transcriptional regulation and localization. We find that Gpd1 and Gpd2 are negatively regulated through phosphorylation by distinct kinases under reciprocal conditions. Gpd2 is phosphorylated by the AMP-activated protein kinase Snf1 to curtail glycerol production when nutrients are limiting. Gpd1, in contrast, is a target of TORC2-dependent kinases Ypk1 and Ypk2. Inactivation of Ypk1 by hyperosmotic shock results in dephosphorylation and activation of Gpd1, accelerating recovery through increased glycerol production. Gpd1 dephosphorylation acts synergistically with its transcriptional upregulation, enabling long-term growth at high osmolarity. Phosphorylation of Gpd1 and Gpd2 by distinct kinases thereby enables rapid adaptation to specific stress conditions. Introduction of phosphorylation motifs targeted by distinct kinases provides a general mechanism for functional specialization of duplicated genes during evolution.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yong Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Grace R
authors.initials: GR
authors.lastname: Jeschke
authors.forename: Françoise M
authors.initials: FM
authors.lastname: Roelants
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Turk
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D020816:Amino Acid Motifs; D005075:Biological Evolution; D015687:Cell Hypoxia / Q000235:genetics; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D005990:Glycerol / Q000378:metabolism; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+) / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C568531:GPD1 protein, S cerevisiae; C568532:GPD2 protein, S cerevisiae; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D011494:Protein Kinases; C071570:SNF1-related protein kinases; C060388:YPK2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C068124:MCK1 protein, S cerevisiae; D005990:Glycerol