Calcium/calmodulin-dependent protein kinases as potential targets of nitric oxide

Tsuyoshi Takata, Jun Kimura, Yukihiro Tsuchiya, Yasuhito Naito, Yasuo Watanabe

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Nitric oxide (NO) synthesis is controlled by Ca 2+/calmodulin (CaM) binding with and kinase-dependent phosphorylation of constitutive NO synthases, which catalyze the formation of NO and l-citrulline from l-arginine. NO operates as a mediator of important cell signaling pathways, such as cGMP signaling cascade. Another mechanism by which NO exerts biological effects is mediated via post-translational modification of redox-sensitive cysteine thiols of proteins. The Ca 2+/CaM-dependent protein kinases (CaM kinases) such as CaM kinase I, CaM kinase II, and CaM kinase IV, are a family of protein kinases which requires binding of Ca 2+/CaM to and subsequent phosphorylation of the enzymes to initiate its activation process. We report other regulation mechanisms of CaM kinases, such as S-glutathionylation of CaM kinase I at Cys 179 and S-nitrosylation of CaM kinase II at Cys 6/30. Such unique post-translational modification of CaMKs by NO shed light on a new area of mutual regulation of NO- and CaM kinases-signals. Based on the novel direct regulation of these kinases, we propose that CaM kinases/NO signaling would be good targets for understanding how they can participate in neuronal physiology and disease.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalNitric Oxide - Biology and Chemistry
Issue number2
Publication statusPublished - 2011 Aug 1
Externally publishedYes


  • Calmodulin-dependent protein kinase
  • Redox regulation
  • S-Glutathionylation
  • S-Nitrosylation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research


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