Abstract
Insulin regulates the activity of the AP-1 (activator protein-1) transcriptional complex in several cell types. One component of the AP-1 complex is the transcription factor Fra-1 (fos-related antigen-1), and we have demonstrated previously that insulin stimulates the expression of Fra-1 mRNA in CHO.T cells [Griffiths, Black, Culbert, Dickens, Shaw, Gillespie and Tavaré (1998) Biochem. J. 335, 19-26]. Here we demonstrate that insulin stimulates the activity of a fra-1 promoter linked to a luciferase reporter gene, indicating that the ability of insulin to induce expression of Fra-1 mRNA is due, at least in part, to an increase in gene transcription. Furthermore, we found that insulin induces the serine phosphorylation of Fra-1 and reduces its mobility during SDS/PAGE as a result of phosphorylation. The ability of insulin to induce the accumulation of Fra-1 mRNA, stimulate the fra-1 promoter and stimulate phosphorylation of Fra-1 all require the mitogen-activated protein (MAP) kinase cascade, which leads to the activation of extracellular-signal-regulated kinase (Erk) 1/2. Consequently, our results demonstrate that the Erk cascade plays a dual role in the co-ordinated regulation of the transcription and the phosphorylation of Fra-1 by insulin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells / drug effects
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Adenoviridae / drug effects
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Adenoviridae / genetics
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Animals
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Base Sequence
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Butadienes / pharmacology
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CHO Cells / drug effects
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Cricetinae
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Doxycycline / pharmacology
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Electrophoresis, Polyacrylamide Gel
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Enzyme Inhibitors / pharmacology
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Genetic Vectors
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Insulin / metabolism*
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Insulin / pharmacology
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MAP Kinase Kinase Kinase 1*
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Mice
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Sequence Data
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Mutation
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Nitriles / pharmacology
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Phosphorylation
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-fos / drug effects
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Proto-Oncogene Proteins c-fos / genetics*
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Proto-Oncogene Proteins c-fos / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcription, Genetic
Substances
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Butadienes
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Enzyme Inhibitors
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Insulin
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Nitriles
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Proto-Oncogene Proteins c-fos
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Recombinant Proteins
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U 0126
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fos-related antigen 1
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Protein Serine-Threonine 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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MAP Kinase Kinase Kinase 1
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Map3k1 protein, mouse
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Doxycycline