The mammalian target of rapamycin-p70 ribosomal s6 kinase but not phosphatidylinositol 3-kinase-Akt signaling is responsible for fibroblast growth factor-9-induced cell proliferation

Lih Yuh C. Wing, Hsiu Mei Chen, Pei Chin Chuang, Meng Hsing Wu, Shaw Jenq Tsai

研究成果: Article同行評審

39 引文 斯高帕斯(Scopus)

摘要

Fibroblast growth factor-9 (FGF9) is a potent mitogen that stimulates normal and cancer cell proliferation though the signaling mechanism is not fully understood. In this study, we aimed to unravel the signaling cascades mediate FGF9 actions in human uterine endometrial stromal cell. Our results demonstrate that the mitogenic effect of FGF9 is transduced via two parallel but additive signaling pathways involving mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase. Activation of mTOR by FGFS induces p70 ribosomal S6 kinase (S6K1) phosphorylation, cyclin expression, and cell proliferation, which are independent of phosphatidylinositol 3-kinase and Akt. Coimmunoprecipitation analysis demonstrates that mTOR physically associates with S6K1 upon FGF9 treatment, whereas ablation of mTOR activity using RNA interference or pharmacological inhibitor blocks S6K1 phosphorylation and cell proliferation induced by FGF9. Further study demonstrates that activation of mTOR is regulated by a phospholipase Cγ-controlled calcium signaling pathway. These studies provide evidence to demonstrate, for the first time, that a novel signaling cascade involving phospholipase Cγ, calcium, mTOR, and S6K1 is activated by FGF9 in a receptor-specific manner.

原文English
頁(從 - 到)19937-19947
頁數11
期刊Journal of Biological Chemistry
280
發行號20
DOIs
出版狀態Published - 2005 五月 20

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 細胞生物學

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