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Upregulation of Egr-1 biosynthesis in human neuroblastoma cells following activation of epidermal growth factor or muscarinic acetylcholine receptors

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The zinc finger transcription factor Egr-1 controls many biological functions in the nervous system, including neuronal plasticity, cell death and proliferation. Egr-1 connects cellular signaling cascades with changes of the gene expression pattern. Here, we show that epidermal growth factor (EGF) and carbachol stimulated the biosynthesis of Egr-1 in human neuroblastoma cells. The analysis of a lentiviral transmitted Egr-1-responsive reporter gene, embedded into the chromatin, revealed that Egr-1-dependent transcription was upregulated following stimulation. The signalling cascade initiated by carbachol involved the muscarinic acetylcholine receptors type I and III and the activation of diacylgycerol-dependent protein kinase C isoforms. Both signaling cascades, initiated by EGF or carbachol, required the activation of extracellular signal-regulated protein kinase ERK. In addition, we observed a striking enhancement of the transcriptional activation potential of the ternary complex factor Elk 1, a key transcriptional regulator of serum response element-driven gene transcription. Incubation of neuroblastoma cells with EGF or carbachol also triggered an upregulation of MAP kinase phosphatase-1 (MKP-1) that dephosphorylates and inactivates ERK in the nucleus. Lentiviral-mediated expression of MKP-1 completely blocked Egr-1 biosynthesis following EGF or carbachol stimulation, indicating that MKP-1 functions as a nuclear shut-of-device of EGF or carbachol-induced Egr-1 gene transcription in neuroblastoma cells.

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Correspondence to Oliver G Rössler.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Epidermal Growth Factor
  • Neuroblastoma Cell
  • Carbachol
  • Human Neuroblastoma Cell
  • Muscarinic Acetylcholine Receptor