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A redox-sensitive t...
A redox-sensitive thiol in Wis1 modulates the fission yeast MAPK response to H2O2 and is the target of a small molecule.
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- Sjölander, Johanna J, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Tarczykowska, Agata, 1989 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Picazo, Cecilia (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Cossio, Itziar (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Redwan, Itedale Namro, 1981 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Gao, Chunxia (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Solano, Carlos (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Toledano, Michel B (author)
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- Grøtli, Morten, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Molin, Mikael, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Sunnerhagen, Per, 1959 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 40:7
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Abstract
Subject headings
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- Oxidation of a highly-conserved cysteine (Cys) residue located in the kinase-activation loop of mitogen-activated protein kinase kinases (MAPKK) inactivates mammalian MKK6. This residue is conserved in the fission yeast MAPKK Wis1, which belongs to the H2O2-responsive MAPK Sty1 pathway. Here, we show that H2O2 reversibly inactivates Wis1 through this residue (C458) in vitro. We found that C458 is oxidized in vivo and that serine substitution of this residue significantly enhances Wis1 activation upon addition of H2O2 The allosteric MAPKK inhibitor, INR119, which binds in a pocket next to the activation loop and C458 prevented the inhibition of Wis1 by H2O2in vitro, and significantly increased Wis1 activation by low levels of H2O2in vivo We propose that oxidation of C458 inhibits Wis1 and that INR119 cancels out this inhibitory effect by binding close to this residue. Kinase inhibition through the oxidation of a conserved Cys residue in MKK6 (C196) is thus conserved in the S. pombe MAPKK Wis1.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Keyword
- MAP kinase Intracellular signaling Redox regulation Conditional activation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sjölander, Johan ...
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Tarczykowska, Ag ...
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Picazo, Cecilia
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Cossio, Itziar
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Redwan, Itedale ...
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Gao, Chunxia
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show more...
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Solano, Carlos
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Toledano, Michel ...
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Grøtli, Morten, ...
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Molin, Mikael, 1 ...
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Sunnerhagen, Per ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medicinal Chemis ...
- Articles in the publication
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Molecular and Ce ...
- By the university
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University of Gothenburg