90-kDa ribosomal S6 kinase 1 is inhibited by S-glutathionylation of its active-site cysteine residue during oxidative stress

Tsuyoshi Takata, Yukihiro Tsuchiya, Yasuo Watanabe

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Previously, we reported that p90-RSK1 phosphorylates neuronal nitric oxide synthase (nNOS) at Ser847 in cells treated with mitogens, leading to the inhibition of NOS activity. Here, we show RSK1 Cys223 glutathionylation limits the activity of the enzyme following an oxidative stimulus and attenuates the nNOS phosphorylation. Treatment of RSK1 with diamide/glutathione results in inactivation of the enzyme in vitro. Mutagenesis studies confirmed that S-glutathionylation of Cys223 is both necessary and sufficient for this inhibition of RSK1. In transfected cells expressing RSK1 and nNOS, treatment with diamide caused a decrease in EGF-induced phosphorylation of nNOS at Ser847. Cells expressing mutant RSK1 (C223S) proved resistant in this regard. Thus, RSK1 Cys223 glutathionylation may contribute to regulate the levels of NO in the brain.

Original languageEnglish
Pages (from-to)1681-1686
Number of pages6
JournalFEBS Letters
Volume587
Issue number11
DOIs
Publication statusPublished - 2013 Jun 5
Externally publishedYes

Keywords

  • 90-kDa ribosomal S6 kinase
  • Glutaredoxin
  • Redox regulation
  • S-Glutathionylation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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