Inhibition of neuronal nitric-oxide synthase by phosphorylation at Threonine1296 in NG108-15 neuronal cells

Tao Song, Naoya Hatano, Kodai Kume, Katsuyoshi Sugimoto, Fuminori Yamaguchi, Masaaki Tokuda, Yasuo Watanabe

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We demonstrate that neuronal nitric-oxide synthase (nNOS) is directly inhibited through the phosphorylation of Thr1296 in NG108-15 neuronal cells. Treatment of NG108-15 cells expressing nNOS with calyculin A, an inhibitor of protein phosphatase 1 and 2A, revealed a dose-dependent inhibition of nNOS enzyme activity with concomitant phosphorylation of Thr1296 residue. Cells expressing a phosphorylation-deficient mutant in which Thr 1296 was changed to Ala proved resistant to phosphorylation and suppression of NOS activity. Mimicking phosphorylation mutant of nNOS in which Thr1296 is changed to Asp showed a significant decrease in nNOS enzyme activity, being competitive with NADPH, relative to the wild-type enzyme. These data suggest that phosphorylation of nNOS at Thr1296 may involve the attenuation of nitric oxide production in neuronal cells through the decrease of NADPH-binding to the enzyme.

Original languageEnglish
Pages (from-to)5658-5662
Number of pages5
JournalFEBS Letters
Volume579
Issue number25
DOIs
Publication statusPublished - Oct 24 2005
Externally publishedYes

Keywords

  • NG108-15 cells
  • Neuronal nitric-oxide synthase
  • Phosphorylation
  • Protein phosphatase

ASJC Scopus subject areas

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

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