Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of its downstream signalling molecules mediated by Ret with the MEN 2B mutation

Hideki Murakami, Toshihide Iwashita, Naoya Asai, Yohei Shimono, Yosuke Iwata, Kumi Kawai, Masahide Takahashi

研究成果: ジャーナルへの寄稿学術論文査読

86 被引用数 (Scopus)

抄録

We compared the intracellular signalling pathways through Ret tyrosine kinase activated by glial cell line-derived neurotrophic factor (GDNF), multiple endocrine neoplasia (MEN) 2A, or MEN 2B mutation. Tyrosine phosphorylation of Grb2-associated binder-1 (Gab1) and activation of phosphatidylinositol 3-kinase (PI 3-kinase) were induced at higher levels by GDNF stimulation or the MEN 2B mutation than by the MEN 2A mutation. Tyrosine-phosphorylated Gab1 was a major component that interacted with the active PI 3-kinase in vivo. In addition, we found that p62Dok and PKB/Akt were phosphorylated in a PI 3-kinase-dependent manner and the levels of their phosphorylation were significantly higher in the MEN 2B transfectant than in the MEN 2A transfectant. Tyrosine phosphorylation of p62Dok resulted in its complex formation with the Ras GTPase-activating protein (Ras-GAP) and the Nck adaptor protein. These findings thus suggested that high levels of activation of PI 3-kinase and of phosphorylation of its downstream signalling molecules may be associated with the clinical phenotype of MEN 2B.

本文言語英語
ページ(範囲)68-75
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
262
1
DOI
出版ステータス出版済み - 19-08-1999

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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