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Title: Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing hormone stimulated gonadotrophs
Authors: Mayer, Sabine I.
Willars, Gary B.
Nishida, Eisuke
Thiel, Gerald
First Published: 1-Dec-2008
Publisher: Wiley-Blackwell
Citation: Journal of Cellular Biochemistry, 2008, 105 (5), pp. 1267-1278.
Abstract: Stimulation of gonadotropin-releasing hormone (GnRH) receptors with the GnRH analogue buserelin enhances expression of the zinc finger transcription factor Egr-1 in a pituitary gonadotroph cell line. The signaling cascade is blocked by overexpression of MAP kinase phosphatase-1 that dephosphorylates extracellular signal-regulated protein kinase in the nucleus. Chromatin immunoprecipitation experiments revealed that the phosphorylated form of Elk-1, a key regulator of gene transcription driven by serum response element (SRE), binds to the 5'-upstream region of the Egr-1 gene in buserelin-stimulated gonadotrophs. Expression of a dominant-negative mutant of Elk-1 completely blocked Egr-1 expression, indicating that Elk-1 connects the intracellular signaling cascade elicited by activation of GnRH receptors with transcription of the Egr-1 gene. GnRH receptor activation additionally induced the phosphorylation of CREB, which in its phosphorylated form bound to the Egr-1 gene. Expression of a dominant-negative mutant of CREB reduced GnRH receptor-induced upregulation of Egr-1 expression, indicating that CREB plays a role in the signaling pathway that regulates Egr-1 expression in gonadotrophs. We further identified the genes encoding basic fibroblast growth factor, tumor necrosis factor , and transforming growth factor β as bona fide target genes of Egr-1 in gonadotrophs. The analysis of gonadotroph cells that express - in addition to GnRH receptors - muscarinic M3 acetylcholine receptors revealed that the nuclear events connecting GnRH receptors and muscarinic M3 acetylcholine receptors with the Egr-1 gene are indistinguishable.
ISSN: 0730-2312
Type: Article
Description: This paper was published as Journal of Cellular Biochemistry, 2008, 105 (5), pp. 1267-1278. It is available from Doi: 10.1002/jcb.21927
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Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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