The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast.
Artikel i vetenskaplig tidskrift, 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

Författare

Michael Thorsen

Göteborgs universitet

Yujun Di

Göteborgs universitet

Carolina Tängemo

Göteborgs universitet

Montserrat Morillas

Doryaneh Ahmadpour

Göteborgs universitet

Charlotte Van der Does

Göteborgs universitet

Annemarie Wagner

Göteborgs universitet

Erik Johansson

Göteborgs universitet

Johan Boman

Göteborgs universitet

Francesc Posas

Robert Wysocki

Markus J. Tamás

Göteborgs universitet

Molecular Biology of the Cell

1059-1524 (ISSN)

Vol. 17 10 4400-10

Ämneskategorier

Fysikalisk kemi

DOI

10.1091/mbc.E06-04-0315

PubMed

16885417