Calcium/calmodulin-dependent protein kinase I inhibits neuronal nitric-oxide synthase activity through serine 741 phosphorylation

Tao Song, Naoya Hatano, Mariko Horii, Hiroshi Tokumitsu, Fuminori Yamaguchi, Masaaki Tokuda, Yasuo Watanabe

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


We demonstrate here that neuronal nitric-oxide synthase (nNOS) is phosphorylated and inhibited by a constitutively active form of Ca 2+/calmodulin (CaM)-dependent protein kinase I (CaM-K I1-293). Substitution of Ser741 to Ala in nNOS blocked the phosphorylation and the inhibitory effect. Mimicking phosphorylation at Ser741 by Ser to Asp mutation resulted in decreased binding of and activation by CaM, since the mutation was within the CaM-binding domain. CaM-K I1-293 gave phosphorylation of nNOS at Ser741 in transfected cells, resulting in 60-70% inhibition of nNOS activity. Wild-type CaM-K I also did phosphorylate nNOS at Ser 741 in transfected cells, but either CaM-K II or CaM-K IV did not. These results raise the possibility of a novel cross-talk between nNOS and CaM-K I through the phosphorylation of Ser741 on nNOS.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalFEBS Letters
Issue number1-3
Publication statusPublished - Jul 16 2004
Externally publishedYes


  • CaM, calmodulin
  • CaM-K I, II, and IV, calcium/calmodulin-dependent protein kinases I, II, and IV
  • CaM-KK, calcium/calmodulin-dependent protein kinase kinase
  • PP2A, protein phosphatase 2A
  • nNOS, neuronal nitric-oxide synthase

ASJC Scopus subject areas

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


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