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

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)19937-19947
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number20
DOIs
Publication statusPublished - 2005 May 20

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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