ERYTHROPOIETIN RECEPTOR AND INTERLEUKIN-2 RECEPTOR USE DIFFERENT DOWNSTREAM SIGNALING PATHWAYS FOR PROLIFERATION AND APOPTOSIS-BLOCK

Erythropoietin (EPO) regulates proliferation and differentiation and p revents apoptosis of erythroid progenitor cells by binding to erythrop oietin receptor (EPOR) expressed on the surface of those cells. The me chanism by which EPO signal is transmitted to the cells through EPOR i s still unclear. In the present study, we introduced and expressed EPO R 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 anal yzed 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-deriv ed cells expressing EPOR (C/EPOR) did not. DNA from C/EPOR cells cultu red in the absence of IL-2 with or without EPO had similar patterns of DNA breakdown. These results suggest that downstream signaling pathwa ys for the cell proliferation and apoptosis-block are, at least, parti ally different between EPOR and IL-2 receptor (IL-2R).