TY - JOUR
T1 - Phosphorylation of neurofibromin by cAMP-dependent protein kinase is regulated via a cellular association of NG,NG-dimethylarginine dimethylaminohydrolase
AU - Tokuo, Hiroshi
AU - Yunoue, Shunji
AU - Feng, Liping
AU - Kimoto, Masumi
AU - Tsuji, Hideaki
AU - Ono, Tomomichi
AU - Saya, Hideyuki
AU - Araki, Norie
N1 - Funding Information:
We thank Dr. I. Izawa, Aichi Cancer Center Research Institute, and Dr. T. Nishi, Department of Neurosurgery, Kumamoto University School of Medicine for valuable discussions, and K. Vrinda, T. Arino and Y. Fukushima for secretarial assistance. This work was supported by grants for Brain Research, Cancer Research, and Kiban Research from the Ministry of Education, Science and Culture of Japan (N.A.), the Ministry of Health and Welfare of Japan (H.S.).
PY - 2001/4/6
Y1 - 2001/4/6
N2 - 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.
AB - 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.
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U2 - 10.1016/S0014-5793(01)02309-2
DO - 10.1016/S0014-5793(01)02309-2
M3 - Article
C2 - 11297733
AN - SCOPUS:0035815448
SN - 0014-5793
VL - 494
SP - 48
EP - 53
JO - FEBS Letters
JF - FEBS Letters
IS - 1-2
ER -