title: FRS2α is essential for the fibroblast growth factor to regulate the mTOR pathway and autophagy in mouse embryonic fibroblasts.
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.
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030-3303, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lin
authors.forename: Yongyou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Leyuan
authors.initials: L
authors.lastname: Liu
authors.forename: Wallace L
authors.initials: WL
authors.lastname: McKeehan
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
authors.forename: Siyang
authors.initials: S
authors.lastname: Song
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001665:Binding Sites; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000166:cytology; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D025941:Protein Interaction Mapping; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D005346:Fibroblast Growth Factors; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C488187:FRS2alpha protein, mouse; C546843:mTOR protein, mouse