Reactive sulfur species impair Ca2+/calmodulin-dependent protein kinase II via polysulfidation

Shoma Araki, Tsuyoshi Takata, Yukihiro Tsuchiya, Yasuo Watanabe

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


We previously reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is inhibited by S-nitrosylation of Cys6 in cells. Herein, we show that polysulfidation of CaMKII at Cys6 limits its enzyme activity following reactive sulfur species (RSS) stimulus. In vitro incubation of CaMKII with the RSS donor, Na2S4, induced the inhibition of the enzyme via its polysulfidation. Treatment with dithiothreitol reversed the polysulfidation and the subsequent inhibition. The inhibition of CaMKII by Na2S4 is competitive with ATP but not with the peptide substrate Syntide-2. In transfected cells expressing CaMKII, the enzyme activity decreased upon treatment with Na2S4, whereas cells expressing mutant CaMKII (C6A) were resistant to this treatment. In addition, the endogenous CaMKII was inhibited by treatment with Na2S4 in RAW264.7 murine macrophage cells. These results suggest a novel regulation of CaMKII by RSS via its Cys6 polysulfidation in cells.

Original languageEnglish
Pages (from-to)550-555
Number of pages6
JournalBiochemical and biophysical research communications
Issue number2
Publication statusPublished - 2019 Jan 8
Externally publishedYes


  • Ca/calmodulin-dependent protein kinase (CaMK)
  • Phosphorylation
  • Polysulfidation
  • Reactive sulfur species (RSS)
  • Redox regulation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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