Erythropoietin activates the receptor in both Rauscher and Friend murine erythroleukemia cells.

Alterations in the expression of two proto-oncogenes, c-myb and c-myc, have been implicated in the differentiation of transformed erythroid cells induced by chemical inducers, such as dimethyl sulfoxide (Me2SO). In the present study, we compared the expression of c-myb and c-myc during erythropoietin (Epo) and Me2SO induction of Rauscher erythroleukemia cells, which differentiate in response to both inducers, and Friend erythroleukemia cells, in which Epo-induced differentiation is blocked. Our results demonstrate that Epo induces specific changes in expression of c-myb and c-myc in both Rauscher and Friend cells. Epo increases c-myc transcript, in contrast to a decreased caused Me2SO, indicating that the biphasic mode of c-myc regulation seen with Me2SO is not required for erythropoiesis. The Epo-induced changes in c-myb and c-myc do not require new protein synthesis, thus identifying these proto-oncogenes as early response genes for Epo. Both cell types also exhibit rapid changes in membrane protein phosphorylation in response to Epo. Since the signal pathway from Epo receptor activation to the nucleus appears equally functional in both Rauscher and Friend cells, the data suggest that the inability of Friend cells to differentiate in response to Epo is due to a block at a later step in the induction process.