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 Tran scription (STAT) proteins become activated following the binding of er ythropoietin (EPO) to immature erythroid cells from the spleens of mic e infected with the anemia strain of Friend virus. STAT1 and STATE pro teins are phosphorylated and translocated to the nucleus in EPO-treate d cells. STAT1 and STATE DNA binding activities were also activated in an EPO-dependent manner. The presence of these STAT proteins in the D NA binding complex was confirmed by Western blot analysis of the prote ins bound to the DNA element in the gel mobility shift assays. This EP O-dependent activation of STAT proteins was maximum within 10 min of e xposure of the cells to 10 units of EPO/ml, the concentration of EPO r equired for maximum STAT activation. The magnitude of the EPO-dependen t STATE activation appeared to be greater than the EPO-dependent activ ation of STAT1. The significance of STAT protein activation in EPO sig nal transduction is discussed.