Opposite effects of inhibitors of mitogen-activated protein kinase pathways on the egr-1 and β-globin expression in erythropoietin-responsive murine erythroleukemia cells

András Schaefer, Ferenc Kósa, Thomas Bittorf, Mária Magócsi, Anette Rosche, Yoandra Ramirez-Chávez, Stefan Marotzki, Hans Marquardt

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The effect of erythropoietin (Epo) on the expression of mitogen-activated protein kinase (MAPK) target genes egr-1 and c-fos was investigated in Epo-responsive murine erythroblastic cell line ELM-I-1. Epo induced a transient rise in egr-1 mRNA without a similar effect on c-fos expression. The induction of egr-1 correlated with a rapid ERK1/2 phosphorylation and was prevented with MEK1/2 inhibitors PD 98059 and UO126. The p38 inhibitor SB 203580 enhanced ERK1/2 phosphorylation and egr-1 mRNA levels. Longer incubations of ELM-I-1 cells with Epo revealed a second later phase of increase in egr-1 expression which was also prevented by MEK1/2 inhibitors, whereas SB 203580 had a stimulatory effect. In contrast, the β-globin mRNA production was enhanced in the presence of PD 98059 and UO126 and reduced by SB 203580. The results suggest a regulatory role of egr-1 expression in Epo signal transduction and provide pharmacological evidence for the negative modulation of differentiation-specific gene expression by the ERK1/2 pathway in murine erythroleukemia cells.

Original languageEnglish
Pages (from-to)223-234
Number of pages12
JournalCellular Signalling
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 2004

Keywords

  • ERK
  • Erythropoietin
  • PD 98059
  • SB 203580
  • UO126
  • c-fos
  • egr-1
  • β-globin

ASJC Scopus subject areas

  • Cell Biology

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