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) 19394586 (eISSN)
Vol. 17 10 4400-10Subject Categories
Physical Chemistry
DOI
10.1091/mbc.E06-04-0315
PubMed
16885417