To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

A redox-sensitive thiol i… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

A redox-sensitive thiol in Wis1 modulates the fission yeast MAPK response to H2O2 and is the target of a small molecule.

Journal article
Authors Johanna J Sjölander
Agata Tarczykowska
Cecilia Picazo
Itziar Cossio
Itedale Namro Redwan
Chunxia Gao
Carlos Solano
Michel B Toledano
Morten Grøtli
Mikael Molin
Per Sunnerhagen
Published in Molecular and Cellular Biology
ISSN 0270-7306
Publication year 2020
Published at Department of Chemistry and Molecular Biology
Language en
Links dx.doi.org/10.1128/MCB.00346-19
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Molecular biology, Biochemistry, Medicinal Chemistry

Abstract

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.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?