Erythropoietin induces the tyrosine phosphorylation, nuclear translocation, and DNA binding of STAT1 and STAT5 in erythroid cells.
We have investigated whether Signal Transducing and Activators of Transcription (STAT) proteins become activated following the binding of erythropoietin (EPO) to immature erythroid cells from the spleens of mice infected with the anemia strain of Friend virus. STAT1 and STAT5 proteins are phosphorylated and translocated to the nucleus in EPO-treated cells. STAT1 and STAT5 DNA binding activities were also activated in an EPO-dependent manner. The presence of these STAT proteins in the DNA binding complex was confirmed by Western blot analysis of the proteins bound to the DNA element in the gel mobility shift assays. This EPO-dependent activation of STAT proteins was maximum within 10 min of exposure of the cells to 10 units of EPO/ml, the concentration of EPO required for maximum STAT activation. The magnitude of the EPO-dependent STAT5 activation appeared to be greater than the EPO-dependent activation of STAT1. The significance of STAT protein activation in EPO signal transduction is discussed.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2287, USA.
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D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D004921:Erythropoietin; D014638:Vanadates; D014443:Tyrosine; D004247:DNA