Inactivation of Ca2+/calmodulin-dependent protein kinase I by S-glutathionylation of the active-site cysteine residue

Toshie Kambe, Tao Song, Tsuyoshi Takata, Naoya Hatano, Yoshiaki Miyamoto, Naohito Nozaki, Yasuhito Naito, Hiroshi Tokumitsu, Yasuo Watanabe

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


We show that Ca2+/calmodulin(CaM)-dependent protein kinase I (CaMKI) is directly inhibited by its S-glutathionylation at the Cys179. In vitro studies demonstrated that treatment of CaMKI with diamide and glutathione results in inactivation of the enzyme, with a concomitant S-glutathionylation of CaMKI at Cys179 detected by mass spectrometry. Mutagenesis studies confirmed that S-glutathionylation of Cys179 is both necessary and sufficient for the inhibition of CaMKI by diamide and glutathione. In transfected cells expressing CaMKI, treatment with diamide caused a reversible decrease in CaMKI activity. Cells expressing mutant CaMKI (179CV) proved resistant in this regard. Thus, our results indicate that the reversible regulation of CaMKI via its modification at Cys179 is an important mechanism in processing calcium signal transduction in cells.

Original languageEnglish
Pages (from-to)2478-2484
Number of pages7
JournalFEBS Letters
Issue number11
Publication statusPublished - Jun 2010
Externally publishedYes


  • Calmodulin-dependent protein kinase I
  • Glutaredoxin
  • Redox regulation
  • S-glutathionylation

ASJC Scopus subject areas

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


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