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PMID: 16885417 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast.

Molecular biology of the cell ·Vol. 17 ·No. 10 ·2006-10-00 ·Pages 4400-10

Thorsen M, Di Y, Tängemo C, Morillas M, Ahmadpour D, Van der Does C, Wagner A, Johansson E, Boman J, Posas F, Wysocki R, Tamás MJ

Abstract

Arsenic is widely distributed in nature and all organisms possess regulatory mechanisms to evade toxicity and acquire tolerance. Yet, little is known about arsenic sensing and signaling mechanisms or about their impact on tolerance and detoxification systems. Here, we describe a novel role of the S. cerevisiae mitogen-activated protein kinase Hog1p in protecting cells during exposure to arsenite and the related metalloid antimonite. Cells impaired in Hog1p function are metalloid hypersensitive, whereas cells with elevated Hog1p activity display improved tolerance. Hog1p is phosphorylated in response to arsenite and this phosphorylation requires Ssk1p and Pbs2p. Arsenite-activated Hog1p remains primarily cytoplasmic and does not mediate a major transcriptional response. Instead, hog1delta sensitivity is accompanied by elevated cellular arsenic levels and we demonstrate that increased arsenite influx is dependent on the aquaglyceroporin Fps1p. Fps1p is phosphorylated on threonine 231 in vivo and this phosphorylation critically affects Fps1p activity. Moreover, Hog1p is shown to affect Fps1p phosphorylation. Our data are the first to demonstrate Hog1p activation by metalloids and provides a mechanism by which this kinase contributes to tolerance acquisition. Understanding how arsenite/antimonite uptake and toxicity is modulated may prove of value for their use in medical therapy.

MeSH Terms
Arsenites/pharmacokinetics,toxicity Cytoplasm/metabolism Gene Expression Regulation, Fungal Membrane Proteins/drug effects,metabolism,physiology Membrane Transport Proteins/physiology Mitogen-Activated Protein Kinases/genetics,physiology Models, Biological Mutation Phosphorylation Protein Transport/drug effects Saccharomyces cerevisiae/drug effects Saccharomyces cerevisiae Proteins/drug effects,genetics,metabolism,physiology Signal Transduction Teratogens/pharmacokinetics,toxicity Threonine Transcription, Genetic
Chemicals
ACR3 protein, S cerevisiae Arsenites FPS1 protein, S cerevisiae Membrane Proteins Membrane Transport Proteins SSK1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Teratogens Threonine HOG1 protein, S cerevisiae Mitogen-Activated Protein Kinases arsenite
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Thorsen Michael
Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden.
Di Yujun
Tängemo Carolina
Morillas Montserrat
Ahmadpour Doryaneh
Van der Does Charlotte
Wagner Annemarie
Johansson Erik
Boman Johan
Posas Francesc
Wysocki Robert
Tamás Markus J
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e06-04-0315
Published
2006-10-00
Epub
2006-00-02
Pages
4400-10
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1635360
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e06-04-0315 PMC Full Text View journal details
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