The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast.
Journal article, 2006

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.

Teratogens

Saccharomyces cerevisiae Proteins

Genetic

Membrane Transport Proteins

Arsenites

Saccharomyces cerevisiae

metabolism

physiology

Signal Transduction

Cytoplasm

Membrane Proteins

physiology

drug effects

genetics

Mutation

Gene Expression Regulation

Threonine

drug effects

Fungal

pharmacokinetics

Models

genetics

Biological

drug effects

pharmacokinetics

physiology

Mitogen-Activated Protein Kinases

physiology

Transcription

toxicity

drug effects

toxicity

metabolism

Phosphorylation

Protein Transport

metabolism

Author

Michael Thorsen

University of Gothenburg

Yujun Di

University of Gothenburg

Carolina Tängemo

University of Gothenburg

Montserrat Morillas

Doryaneh Ahmadpour

University of Gothenburg

Charlotte Van der Does

University of Gothenburg

Annemarie Wagner

University of Gothenburg

Erik Johansson

University of Gothenburg

Johan Boman

University of Gothenburg

Francesc Posas

Robert Wysocki

Markus J. Tamás

University of Gothenburg

Molecular Biology of the Cell

1059-1524 (ISSN)

Vol. 17 10 4400-10

Subject Categories

Physical Chemistry

DOI

10.1091/mbc.E06-04-0315

PubMed

16885417

More information

Created

10/10/2017