Intracellular mechanism by which arsenite activates the yeast stress MAPK Hog1

Molecular Biology of the Cell
Jongmin Lee, David E Levin

Abstract

Stress-activated MAPKs (SAPKs) respond to a wide variety of stressors. In most cases, the pathways through which specific stress signals are transmitted to the SAPKs are not known. In this study, we delineate the intracellular signaling pathway by which the trivalent toxic metalloid arsenite [As(III)] activates the yeast SAPK Hog1. We demonstrate that, to activate Hog1, As(III) must enter the cell through the glycerol channel Fps1 and must be metabolized to methyl arsenite [MAs(III)] by the dimeric methyltransferase Mtq2:Trm112. We found that Mtq2:Trm1 displays SAM-dependent methyltransferase activity toward both As(III) and MAs(III). Additionally, we present genetic and biochemical evidence that MAs(III), but not As(III), is a potent inhibitor of the protein tyrosine phosphatases (Ptp2 and Ptp3) that normally maintain Hog1 in an inactive state. Inhibition of Ptp2 and Ptp3 by MAs(III) results in elevated Hog1 phosphorylation without activation of the protein kinases that act upstream of the SAPK and raises the possibility that other Hog1-activating stressors act intracellularly at different points along the canonical Hog1 activation pathway. Finally, we show that arsenate [As(V)], a pentavalent form of arsenic, also activates H...Continue Reading

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Citations

Sep 20, 2018·Molecular Biology of the Cell·Li Liu, David E Levin
Nov 27, 2018·PLoS Neglected Tropical Diseases·James A ThomasDavid Horn
Nov 1, 2018·Current Genetics·Jongmin LeeDavid E Levin
Nov 28, 2019·Science Signaling·Angel Guerra-MorenoJohn Hanna
Aug 6, 2019·Frontiers in Cellular and Infection Microbiology·Alison M Day, Janet Quinn
Mar 20, 2019·Molecular and Cellular Biology·Marco JochemJohn Hanna
May 12, 2020·Fungal Biology·Alene Alder-RangelDrauzio E N Rangel
Aug 3, 2021·Frontiers in Microbiology·Shaowei WangShi-Hong Zhang
Dec 12, 2021·Critical Reviews in Microbiology·Hajar YaakoubNicolas Papon

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Methods Mentioned

BETA
nuclear translocation
PCR
fluorescence microscopy
protein kinase assay
phosphatase assay
protein
affinity purification
coIP
protein kinase
Protein Assay

Software Mentioned

Excel
ImageJ

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