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Göteborgs universitets publikationer

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

Författare och institution:
Michael Thorsen (Institutionen för cell- och molekylärbiologi); Yujun Di (Institutionen för cell- och molekylärbiologi); Carolina Tängemo (Institutionen för cell- och molekylärbiologi); Montserrat Morillas (-); Doryaneh Ahmadpour (Institutionen för cell- och molekylärbiologi); Charlotte Van der Does (Institutionen för cell- och molekylärbiologi); Annemarie Wagner (Institutionen för kemi); Erik Johansson (Institutionen för cell- och molekylärbiologi); Johan Boman (Institutionen för kemi); Francesc Posas (-); Robert Wysocki (-); Markus J. Tamás (Institutionen för cell- och molekylärbiologi)
Publicerad i:
Molecular biology of the cell, 17 ( 10 ) s. 4400-10
Artikel, refereegranskad vetenskaplig
Sammanfattning (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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Kemi ->
Fysikalisk kemi
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
Postens nummer:
Posten skapad:
2007-10-15 15:50
Posten ändrad:
2011-01-20 10:00

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