Abstract
Basic fibroblast growth factor (FGF-2) is a member of a family of polypeptides that have roles in a wide range of biological processes. To determine why different cell types show distinct responses to treatment with FGF-2, the array of FGF receptors present on the surface of a cell which differentiates in response to FGF-2 (PC12 cells) was compared with that present on the surface of a cell that proliferates in response to FGF-2 (Swiss 3T3 fibroblasts). Both cell types express exclusively FGFR1, suggesting that there are cell type-specific FGFR1 signaling pathways. Since mitogen-activated protein kinases function as mediators of cellular responses to a variety of stimuli, the roles of these proteins in FGF-mediated responses were examined. FGF-2 activates extracellular signal-regulated kinases with similar kinetics in both fibroblasts and PC12 cells, and a specific inhibitor of extracellular signal-regulated kinase activation blocks differentiation but has little effect on proliferation. In contrast, while p38 mitogen-activated protein kinase is activated weakly and transiently in PC12 cells treated with FGF-2, a much stronger and sustained activation of this kinase is seen in FGF-2-treated fibroblasts. Furthermore, specific inhibitors of this kinase block proliferation but have no effect on differentiation. This effect on proliferation is specific for FGF-2 since the same concentrations of inhibitors have little or no effect on proliferation induced by serum.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Butadienes / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Differentiation / drug effects
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Cell Division / drug effects*
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Fibroblast Growth Factor 2 / pharmacology*
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Flavonoids / pharmacology
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Intracellular Signaling Peptides and Proteins
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Mice
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Nitriles / pharmacology
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PC12 Cells
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Protein Serine-Threonine Kinases / metabolism
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Rats
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / analysis
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Receptors, Fibroblast Growth Factor / metabolism
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Signal Transduction
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Time Factors
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p38 Mitogen-Activated Protein Kinases
Substances
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Butadienes
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Enzyme Inhibitors
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Flavonoids
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Intracellular Signaling Peptides and Proteins
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Nitriles
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Receptors, Fibroblast Growth Factor
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U 0126
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Fibroblast Growth Factor 2
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MAP-kinase-activated kinase 2
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Fgfr1 protein, mouse
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Fgfr1 protein, rat
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one