PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin

Liping Feng, Shunji Yunoue, Hiroshi Tokuo, Tatsuya Ozawa, Dongwei Zhang, Siriporn Patrakitkomjorn, Toru Ichimura, Hideyuki Saya, Norie Araki

研究成果: Article査読

42 被引用数 (Scopus)

抄録

Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell proliferation. Therefore, regulation of the function of neurofibromin is heavily involved in cell growth and differentiation. In the present study, we identified a novel cellular neurofibromin-associating protein, 14-3-3, which belongs to a highly conserved family of proteins that regulate intracellular signal transduction events in all eukaryotic cells. The interaction of 14-3-3 is mainly directed to the C-terminal domain (CTD) of neurofibromin, and the cAMP-dependent protein kinase (PKA)-dependent phosphorylation clustered on CTD-Ser (2576, 2578, 2580, 2813) and Thr (2556) is required for the interaction. Interestingly, the increased phosphorylation and association of 14-3-3 negatively regulate the function of neurofibromin. These findings indicate that PKA phosphorylation followed by 14-3-3 protein interaction may modulate the biochemical and biological functions of neurofibromin.

本文言語English
ページ(範囲)275-282
ページ数8
ジャーナルFEBS Letters
557
1-3
DOI
出版ステータスPublished - 2004 1 16
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 構造生物学
  • 生化学
  • 分子生物学
  • 遺伝学
  • 細胞生物学

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