Role of a truncated erythropoietin receptor for erythroid differentiation

Erythropoietin (EPO) is a cytokine that regulates erythropoiesis through the EPO receptor (EPOR). We reported previously that erythroid progenitor cells express both a full-length and a truncated form of EPOR (EPOR-F and EPOR-Tph). EPOR-Tph cannot transmit growth signals and acts as a dominant negative regulator against EPOR-F-mediated signals for cell survival and growth. Upon transfection of EPOR-F in a cell line, Ba/F3, beta-globin accumulation, which is considered to be a marker of erythroid-differentiation, is inducible in the transformants. We show here that the co-expression of EPOR-Tph in EPOR-F-transformants does not inhibit and rather upregulates the beta-globin induction while inhibiting survival and growth of the transformants. These data suggest that, in contrast to survival and growth signals, EPOR-Tph acts as a positive regulator for erythroid-differentiation signals in erythroid progenitor cells.