Phosphorylation of neurofibromin by cAMP-dependent protein kinase is regulated via a cellular association of NG,NG-dimethylarginine dimethylaminohydrolase

Hiroshi Tokuo, Shunji Yunoue, Liping Feng, Masumi Kimoto, Hideaki Tsuji, Tomomichi Ono, Hideyuki Saya, Norie Araki

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


The neurofibromatosis type 1 (NF1) tumor suppressor (neurofibromin) is thought to play crucial roles in cellular Ras- and cAMP-dependent kinase (PKA)-associated signals. In this study, we identified a cellular neurofibromin-associating protein, NG,NG-dimethylarginine dimethylaminohydrolase (DDAH) that is known as a cellular NO/NOS regulator. The interaction of DDAH was mainly directed to the C-terminal domain (CTD) and to the cysteine/serine-rich domain (CSRD) of neurofibromin, coinciding with the regions containing specific PKA phosphorylation sites. DDAH increased PKA phosphorylation of native neurofibromin in a dose-dependent manner, especially affecting the phosphorylation of CSRD. These findings suggest that the PKA accessibility of neurofibromin was regulated via DDAH interaction, and this regulation may modulate the cellular function of neurofibromin that is implicated in NF1-related pathogenesis.

Original languageEnglish
Pages (from-to)48-53
Number of pages6
JournalFEBS Letters
Issue number1-2
Publication statusPublished - 2001 Apr 6
Externally publishedYes


  • N,N-dimethylarginine dimethylaminohydrolase (DDAH)
  • Neurofibromatosis Type 1 (NF1)
  • Neurofibromatosis type 1
  • Neurofibromin
  • cAMP-dependent protein kinase (PKA)

ASJC Scopus subject areas

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


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