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

doi:10.1016/S0014-5793(01)02309-2

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

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

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

Abstract

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, N^G,N^G-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 language	English
Pages (from-to)	48-53
Number of pages	6
Journal	FEBS Letters
Volume	494
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-5793(01)02309-2
Publication status	Published - 06-04-2001
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(01)02309-2

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

abstract = "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.",

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

note = "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.).",

year = "2001",

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day = "6",

doi = "10.1016/S0014-5793(01)02309-2",

language = "English",

volume = "494",

pages = "48--53",

journal = "FEBS Letters",

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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

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

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