INDUCTION OF ERYTHROID-SPECIFIC GENE-EXPRESSION IN LYMPHOID-CELLS

Erythropoietin (Epo) is a cytokine which specifically regulates differ entiation and proliferation of erythroid progenitor cells. We report h ere that Epo receptor expressed in interleukin 3-dependent lymphoid Ba /F3 cells transmits both differentiation and growth signals. Epo stimu lation of these cells leads to activation of transcription and/or tran slation of the erythroid-specific transcription factors GATA-1 and SCL , followed by the accumulation of both alpha- and beta-globin chains. These results suggest that expression and activation of the Epo recept or regulates erythroid-specific gene expression and might play a role in determining a cell lineage in vivo and that GATA-1 and SCL may exer t their effects after Epo binds to its receptor. It was further found that chimeric receptors composed of extracellular domains of Epo recep tor and cytoplasmic domains of interleukin 2 or interleukin 3 receptor s could also induce erythroid-specific gene expression in Ba/F3 cells. Taking these data together with previous observations, we conclude th at interaction of the extracellular domains of the Epo receptor with o ther membrane components is essential for transmission of both the ery throid differentiation and the growth signals.