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Elucidation of a signaling pathway induced by FGF-2 leading to uPA gene expression in NIH 3T3 fibroblasts

Item Type:Article
Title:Elucidation of a signaling pathway induced by FGF-2 leading to uPA gene expression in NIH 3T3 fibroblasts
Creators Name:Besser, D. and Presta, M. and Nagamine, Y.
Abstract:Fibroblast growth factors (FGFs) play a role in biological processes such as cell growth and development, angiogenesis, and wound healing. Several genes have been shown to be induced by FGFs, but the underlying mechanisms have not been elucidated. We investigated the effect of FGF-2 (basic FGF) on the urokinase-type plasminogen activator (uPA) gene in NIH 3T3 fibroblasts. We found that the uPA gene is transcriptionally induced by FGF-2 as well as by 12-O-tetradecanoylphorbol-13 -acetate involving a PEA3/AP1 element located 2.4 kb upstream of the transcription initiation site; neither induction requires ongoing protein synthesis. Unlike 12-O-tetradecanoylphorbol-13-acetate induction, FGF-2 induction was not impaired by protein kinase C down-regulation. Analyses of various signaling molecules by Western blotting, extracellular signal-regulated kinase (ERK) activity assays, and transient transfection assays (cotransfection of a uPA-reporter gene construct with expression vectors for wild-type or dominant negative type of these molecules or for ERK-specific protein phosphatase MKP-1) showed that a Ras/Raf-1/MEK/ERK-2/JunD pathway is induced by FGF-2 and 12-O-tetradecanoylphorbol-13-acetate, leading to the activation of the uPA gene.
Keywords:3T3 Cells, Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Enzyme Activation, Fibroblast Growth Factor 2, Enzymologic Gene Expression Regulation, Molecular Sequence Data, Genetic Promoter Regions, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-raf, Signal Transduction, Tetradecanoylphorbol Acetate, Transcription Factor AP-1, Urokinase-Type Plasminogen Activator, ras Proteins, Animals, Mice
Source:Cell Growth & Differentiation
ISSN:1044-9523
Publisher:American Association for Cancer Research (U.S.A.)
Volume:6
Number:8
Page Range:1009-1017
Date:August 1995
Official Publication:http://cgd.aacrjournals.org/cgi/content/abstract/6/8/1009
PubMed:View item in PubMed

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