A POSSIBLE INVOLVEMENT OF STAT5 IN ERYTHROPOIETIN-INDUCED HEMOGLOBIN-SYNTHESIS

Erythropoietin (EPO) and its cell surface receptor (EPOR) play central roles in the proliferation and differentiation of mammalian erythroid progenitor cells. Recently both the tyrosine residues in the EPOR res ponsible for the activation of Stat5 and the role of Stat5 for EPO-dep endent cell proliferation have been shown. Here, we describe the roles of Stat5 and of these tyrosine residues in the EPOR in the erythroid differentiation of murine hematopoietic cell line SKT6 which produces hemoglobin in response to EPO. Chimeric receptors carrying the extrace llular domain of the EGF receptor and the intracellular domain of the EPOR were introduced into SKT6 cells. Like EPO, EGF equally activated Stat5 and induced hemoglobin. Activation of Stat5 and hemoglobin expre ssion by EGF were markedly impaired in cells expressing the tyrosine m utated chimeric receptors. In addition, ectopic expression of the prol actin receptor, another cytokine receptor that activates Stat5, led to hemoglobin synthesis. Finally, hemoglobin synthesis was severely inhi bited by overexpressing a dominant negative form of Stat5. These resul ts collectively suggest that Stat5 plays a role in EPO-mediated hemogl obin synthesis in SKT6 cells. (C) 1997 Academic Press.