Erythropoietin receptor and interleukin-2 receptor use different downstream signaling pathways for proliferation and apoptosis-block.

Erythropoietin (EPO) regulates proliferation and differentiation and prevents apoptosis of erythroid progenitor cells by binding to erythropoietin receptor (EPOR) expressed on the surface of those cells. The mechanism by which EPO signal is transmitted to the cells through EPOR is still unclear. In the present study, we introduced and expressed EPOR in an interleukin-3 (IL-3) dependent pro-B cell line, BAF-B03 and an interleukin-2 (IL-2)-dependent cytotoxic T cell line, CTLL-2 and analyzed their growth response to EPO and the DNA breakdown characteristic to apoptosis after deprivation of the growth factor. BAF-B03-derived cells expressing EPOR proliferated in response to EPO but CTLL-2-derived cells expressing EPOR (C/EPOR) did not. DNA from C/EPOR cells cultured in the absence of IL-2 with or without EPO had similar patterns of DNA breakdown. These results suggest that downstream signaling pathways for the cell proliferation and apoptosis-block are, at least, partially different between EPOR and IL-2 receptor (IL-2R).