title: Dissection of the HOG pathway activated by hydrogen peroxide in Saccharomyces cerevisiae.
abstract: Cells usually cope with oxidative stress by activating signal transduction pathways. In the budding yeast Sacchromyces cerevisiae, the high osmolarity glycerol (HOG) pathway has long been implicated in transducing the oxidative stress-induced signal, but the underlying mechanisms are not well defined. Based on phosphorylation of the mitogen-activated protein kinase (MAPK) Hog1, we reveal that the signal from hydrogen peroxide (H2O2) flows through Ssk1, the response regulator of the two-component system of the HOG pathway. Downstream signal transduction into the HOG MAPK cascade requires the MAP kinase kinase kinase (MAP3K) Ssk2 but not its paralog Ssk22 or another MAP3K Ste11 of the pathway, culminating in Hog1 phosphorylation via the MAP2K Pbs2. When overexpressed, Ssk2 is also activated in an Ssk1-independent manner. Unlike in mammals, H2O2does not cause endoplasmic reticulum stress, which can activate Hog1 through the conventional unfolded protein response. Hog1 activated by H2O2is retained in the cytoplasm, but is still able to activate the cAMP- or stress-responsive elements by unknown mechanisms.
authors.affiliation: Department of Pharmacology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: An
authors.affiliation: Division of Interdisciplinary Program of EcoCreative, College of Natural Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Yeji
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Division of Interdisciplinary Program of EcoCreative, College of Natural Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Eunyong
authors.initials: E
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Ewha Womans University, Seoul, Korea.|Division of Interdisciplinary Program of EcoCreative, College of Natural Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Wonja
authors.initials: W
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Ajou University, Suwon, Korea.
authors.forename: Eunpyo
authors.initials: E
authors.lastname: Moon
authors.affiliation: Department of Pharmacology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Wankee
authors.initials: W
authors.lastname: Kim
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005990:Glycerol / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D005990:Glycerol