HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 20, 19937-19947, May 20, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/20/19937    most recent M411865200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wing, L.-Y. C. Articles by Tsai, S.-J. Search for Related Content PubMed PubMed Citation Articles by Wing, L.-Y. C. Articles by Tsai, S.-J. Social Bookmarking                      What's this?

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||, and Shaw-Jenq Tsai¶**

From the Department of Physiology, the ^¶Institute of Basic Medical Sciences, and the ^||Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, Republic of China

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 C-controlled calcium signaling pathway. These studies provide evidence to demonstrate, for the first time, that a novel signaling cascade involving phospholipase C, calcium, mTOR, and S6K1 is activated by FGF9 in a receptor-specific manner.

Received for publication, October 19, 2004 , and in revised form, March 2, 2005.

^* This work was supported by National Science Council of the Republic of China, Taiwan, Grants NSC 92-2320-B006-080 (to S.-J. T.) and NSC 92-2320-B006-038 (to L.-Y. C. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence may be addressed: Dept. of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China. Fax: 886-6-236-2780; E-mail: wing{at}mail.ncku.edu.tw. ** To whom correspondence may be addressed: Dept. of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China. Fax: 886-6-236-2780; E-mail: seantsai{at}mail.ncku.edu.tw.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Vazquez-Martin, C. Oliveras-Ferraros, R. Colomer, J. Brunet, and J. A. Menendez Low-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb(R)) in human breast carcinoma cells Ann. Onc., June 1, 2008; 19(6): 1097 - 1109. [Abstract] [Full Text] [PDF]

				M. Marzec, X. Liu, M. Kasprzycka, A. Witkiewicz, P. N. Raghunath, M. El-Salem, E. Robertson, N. Odum, and M. A. Wasik IL-2- and IL-15-induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes Blood, February 15, 2008; 111(4): 2181 - 2189. [Abstract] [Full Text] [PDF]

				C. Brewer, N. Yeager, and A. Di Cristofano Thyroid-Stimulating Hormone Initiated Proliferative Signals Converge In vivo on the mTOR Kinase without Activating AKT Cancer Res., September 1, 2007; 67(17): 8002 - 8006. [Abstract] [Full Text] [PDF]

				P. P. Kayampilly and K. M. J. Menon Follicle-Stimulating Hormone Increases Tuberin Phosphorylation and Mammalian Target of Rapamycin Signaling through an Extracellular Signal-Regulated Kinase-Dependent Pathway in Rat Granulosa Cells Endocrinology, August 1, 2007; 148(8): 3950 - 3957. [Abstract] [Full Text] [PDF]

				H. Lu, P. W. M. Fedak, X. Dai, C. Du, Y.-Q. Zhou, M. Henkelman, P. S. Mongroo, A. Lau, H. Yamabi, A. Hinek, et al. Integrin-Linked Kinase Expression Is Elevated in Human Cardiac Hypertrophy and Induces Hypertrophy in Transgenic Mice Circulation, November 21, 2006; 114(21): 2271 - 2279. [Abstract] [Full Text] [PDF]

				P.-C. Chuang, H. S. Sun, T.-M. Chen, and S.-J. Tsai Prostaglandin E2 Induces Fibroblast Growth Factor 9 via EP3-Dependent Protein Kinase C{delta} and Elk-1 Signaling Mol. Cell. Biol., November 15, 2006; 26(22): 8281 - 8292. [Abstract] [Full Text] [PDF]

				J. Wang, N. Wang, J. Xie, S. C. Walton, R. L. McKown, R. W. Raab, P. Ma, S. L. Beck, G. L. Coffman, I. M. Hussaini, et al. Restricted epithelial proliferation by lacritin via PKC{alpha}-dependent NFAT and mTOR pathways J. Cell Biol., August 28, 2006; 174(5): 689 - 700. [Abstract] [Full Text] [PDF]

				P. Wlodarski, M. Kasprzycka, X. Liu, M. Marzec, E. S. Robertson, A. Slupianek, and M. A. Wasik Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum Cancer Res., September 1, 2005; 65(17): 7800 - 7808. [Abstract] [Full Text] [PDF]