PMID- 15760907
OWN - NLM
STAT- MEDLINE
DCOM- 20050708
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 20
DP  - 2005 May 20
TI  - 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.
PG  - 19937-47
AB  - 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 FGF9 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 Cgamma-controlled calcium signaling pathway. These studies 
      provide evidence to demonstrate, for the first time, that a novel signaling 
      cascade involving phospholipase Cgamma, calcium, mTOR, and S6K1 is activated by 
      FGF9 in a receptor-specific manner.
FAU - Wing, Lih-Yuh C
AU  - Wing LY
AD  - Department of Physiology, National Cheung Kung University, Tainan, Taiwan, 
      Republic of China. wing@mail.ncku.edu.tw
FAU - Chen, Hsiu-Mei
AU  - Chen HM
FAU - Chuang, Pei-Chin
AU  - Chuang PC
FAU - Wu, Meng-Hsing
AU  - Wu MH
FAU - Tsai, Shaw-Jenq
AU  - Tsai SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050310
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (FGF9 protein, human)
RN  - 0 (Fibroblast Growth Factor 9)
RN  - 0 (Mitogens)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Endometrium/cytology/drug effects/metabolism
MH  - Female
MH  - Fibroblast Growth Factor 9
MH  - Fibroblast Growth Factors/*pharmacology
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogens/pharmacology
MH  - Models, Biological
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases
MH  - ras Proteins/metabolism
EDAT- 2005/03/12 09:00
MHDA- 2005/07/09 09:00
CRDT- 2005/03/12 09:00
PHST- 2005/03/12 09:00 [pubmed]
PHST- 2005/07/09 09:00 [medline]
PHST- 2005/03/12 09:00 [entrez]
AID - S0021-9258(20)61781-1 [pii]
AID - 10.1074/jbc.M411865200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 May 20;280(20):19937-47. doi: 10.1074/jbc.M411865200. Epub 2005 
      Mar 10.