Abstract
The zinc finger protein early growth response 1 (Egr-1) is a transcriptional activator involved in the regulation of growth and differentiation. We show here that a constitutive active mutant of mitogen-activated kinase kinase-1 (MAPKK-1) strongly stimulates the activity of the Egr-1 promoter, thus explaining the effects of mitogens upon Egr-1 mRNA and protein levels. Moreover, we show that a constitutive active MAPKK-1 leads to an increase in the biological activity of Egr-1 to activate transcription. We conclude that the signaling pathway involving mitogen-activated protein kinase/extracellular signal-regulated protein kinase has a dual impact on the biology of Egr-1 by controlling the transcription of the Egr-1 gene and the transcriptional activity of the Egr-1 protein.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Early Growth Response Protein 1
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Gene Expression Regulation*
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Humans
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Immediate-Early Proteins*
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Luciferases / metabolism
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MAP Kinase Kinase 1
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MAP Kinase Signaling System*
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / physiology
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinase Kinases / genetics
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Mitogen-Activated Protein Kinase Kinases / physiology
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / physiology*
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Mutagenesis, Site-Directed
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Transfection
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beta-Galactosidase / genetics
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beta-Galactosidase / metabolism
Substances
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DNA-Binding Proteins
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EGR1 protein, human
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Early Growth Response Protein 1
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Immediate-Early Proteins
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Transcription Factors
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Luciferases
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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 1
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MAP2K1 protein, human
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Mitogen-Activated Protein Kinase Kinases
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beta-Galactosidase