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

FEBS Letters

Araki, Norie¹  Kimoto, Masumi³  Feng, Liping¹  Yunoue, Shunji¹  Tokuo, Hiroshi¹  Ono, Tomomichi²  Tsuji, Hideaki³  Saya, Hideyuki¹ 

[1] Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan;Department of Dermatology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan;Department of Nutritional Science, Okayama Prefectural University, Kuboki, Soja, Okayama 719-1137, Japan

关键词: Neurofibromatosis type 1;    Neurofibromatosis Type 1 (NF1);    Neurofibromin;    cAMP-dependent protein kinase (PKA);    N G;    N G-dimethylarginine dimethylaminohydrolase (DDAH);   

DOI  :  10.1016/S0014-5793(01)02309-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown