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 inhibite d basal- as well as erythropoietin-stimulated proliferation of the ery throid cell line J2E. In addition, it enhanced the antiproliferative e ffect of sodium butyrate. Although rapamycin suppressed erythroid cell division, it did not affect terminal differentiation induced by eryth ropoietin or sodium butyrate. The proliferative status of J2E cells co rrelated well with the activity of the ribosomal S6 kinase p70(S6k), e nzyme effectively blocked by rapamycin. It was concluded from this stu dy that erythroid maturation proceeded normally despite the rapamycin- induced inhibition of mitosis and of p70(S6k) activity. These data pro vide further evidence that separate signalling pathways for proliferat ion and differentiation exist in erythroid cells.