Opposite effects of inhibitors of mitogen-activated protein kinase pathways on the egr-1 and β-globin expression in erythropoietin-responsive murine erythroleukemia cells
- Resource Type
- Authors
- Yoandra Ramirez-Chávez; András Schaefer; Thomas Bittorf; Ferenc Kósa; Anette Rosche; Stefan Marotzki; Mária Magócsi; Hans Marquardt
- Source
- Cellular Signalling. 16:223-234
- Subject
- MAPK/ERK pathway
MAP Kinase Signaling System
Pyridines
SB 203580
p38 mitogen-activated protein kinases
Biology
Immediate-Early Proteins
Mice
chemistry.chemical_compound
hemic and lymphatic diseases
Nitriles
Gene expression
Butadienes
Tumor Cells, Cultured
medicine
Animals
Enzyme Inhibitors
Phosphorylation
Protein kinase A
Erythropoietin
Early Growth Response Protein 1
Flavonoids
Mitogen-Activated Protein Kinase Kinases
Imidazoles
Cell Biology
Molecular biology
Globins
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
body regions
chemistry
Mitogen-activated protein kinase
biology.protein
Leukemia, Erythroblastic, Acute
Mitogen-Activated Protein Kinases
Signal transduction
Proto-Oncogene Proteins c-fos
hormones, hormone substitutes, and hormone antagonists
Transcription Factors
medicine.drug
- Language
- ISSN
- 0898-6568
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.