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Int J Biol Sci 2011; 7(8):1114-1121. doi:10.7150/ijbs.7.1114

Research Paper

FRS2α is Essential for the Fibroblast Growth Factor to Regulate the mTOR Pathway and Autophagy in Mouse Embryonic Fibroblasts

Xiang Lin1,2,#, Yongyou Zhang1,*, Leyuan Liu1, Wallace L. McKeehan1, Yuemao Shen2, Siyang Song2,✉, Fen Wang1,✉

1. Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX;
2. The Key Laboratory of Education Ministry for Cell Biology and Tumor Cell Engineering; School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P. R. China.
# Current address: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, 350108, P. R. China;
* Current address: Howard Hughes Medical Institute Laboratory, Wolstein Research Building, 2103 Cornell Road, Cleveland, OH 44106-7285.

Abstract

Although the fibroblast growth factor (FGF) signaling axis plays important roles in cell survival, proliferation, and differentiation, the molecular mechanism underlying how the FGF elicits these diverse regulatory signals is not well understood. By using the Frs2α null mouse embryonic fibroblast (MEF) in conjunction with inhibitors to multiple signaling pathways, here we report that the FGF signaling axis activates mTOR via the FGF receptor substrate 2α (FRS2α)-mediated PI3K/Akt pathway, and suppresses autophagy activity in MEFs. In addition, the PI3K/Akt pathway regulated mTOR is crucial for the FGF signaling axis to suppress autophagy in MEFs. Since autophagy has been proposed to play important roles in cell survival, proliferation, and differentiation, the findings suggest a novel mechanism for the FGF signaling axis to transmit regulatory signals to downstream effectors.

Keywords: FGF, autophagy, mouse embryonic fibroblast, receptor tyrosine kinase, cell signaling.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Lin X, Zhang Y, Liu L, McKeehan WL, Shen Y, Song S, Wang F. FRS2α is Essential for the Fibroblast Growth Factor to Regulate the mTOR Pathway and Autophagy in Mouse Embryonic Fibroblasts. Int J Biol Sci 2011; 7(8):1114-1121. doi:10.7150/ijbs.7.1114. Available from http://www.ijbs.com/v07p1114.htm