Inhibition of proliferation but not erythroid differentiation of J2E cells by rapamycin

During erythropoiesis, replication and maturation are tightly coupled processes. Here, we show that the immunosuppressant rapamycin inhibited basal- as well as erythropoietin-stimulated proliferation of the erythroid cell line J2E. In addition, it enhanced the antiproliferative effect of sodium butyrate. Although rapamycin suppressed erythroid cell division, it did not affect terminal differentiation induced by erythropoietin or sodium butyrate. The proliferative status of J2E cells correlated well with the activity of the ribosomal S6 kinase p70(S6k), enzyme effectively blocked by rapamycin. It was concluded from this study that erythroid maturation proceeded normally despite the rapamycin-induced inhibition of mitosis and of p70(S6k) activity. These data provide further evidence that separate signalling pathways for proliferation and differentiation exist in erythroid cells.