A Redox-Sensitive Thiol in Wis1 Modulates the Fission Yeast Mitogen-Activated Protein Kinase Response to H2O2 and Is the Target of a Small Molecule

Sjölander, Johanna J. (author): Göteborgs universitet,University of Gothenburg

Tarczykowska, Agata (author): Göteborgs universitet,University of Gothenburg

Picazo Campos, Cecilia, 1987 (author): Göteborgs universitet,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology

Redwan, Itedale Namro, 1981 (author): Göteborgs universitet,University of Gothenburg

Toledano, Michel B. (author): Université Paris-Saclay,University Paris-Saclay

Grötli, Morten, 1966 (author): Göteborgs universitet,University of Gothenburg

Molin, Mikael, 1973 (author): Chalmers tekniska högskola,Chalmers University of Technology,Göteborgs universitet,University of Gothenburg

Sunnerhagen, Per, 1959 (author): Göteborgs universitet,University of Gothenburg

(creator_code:org_t)

Related links:: https://research.cha... (primary) (free); show more...; https://doi.org/10.1...; https://research.cha...; show less...

Abstract Subject headings

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 Schizosaccharomyces pombe 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 replacement 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.

NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

By the author/editor: Sjölander, Johan ...; Tarczykowska, Ag ...; Picazo Campos, C ...; Cossio, Itziar; Redwan, Itedale ...; Gao, Chunxia; show more...; Solano, Carlos; Toledano, Michel ...; Grötli, Morten, ...; Molin, Mikael, 1 ...; Sunnerhagen, Per ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medicinal Chemis ...

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