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 mitogenactivated 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 mitogenactivated protein kinase/extracellular signalregulated 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.
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