Erythropoietin receptor signals both proliferation and erythroid-specific differentiation.
Ectopic expression of the erythropoietin receptor (EPO-R) in Ba/F3, an interleukin 3-dependent progenitor cell line, confers EPO-dependent cell growth. To examine whether the introduced EPO-R could affect differentiation, we isolated Ba/F3-EPO-R subclones in interleukin 3 and assayed for the induction of beta-globin mRNA synthesis after exposure to EPO. Detection of beta-globin mRNA was observed within 3 days of EPO treatment, with peak levels accumulating after 10 days. When EPO was withdrawn, expression of beta-globin mRNA persisted in most clones, suggesting that commitment to erythroid differentiation had occurred. Although EPO-R expression also supports EPO-dependent proliferation of CTLL-2, a mature T-cell line, those cells did not produce globin transcripts, presumably because they lack requisite cellular factors involved in erythrocyte differentiation. We conclude that the EPO-R transmits signals important for both proliferation and differentiation along the erythroid lineage.
Liboi
E
E
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
Carroll
M
M
D'Andrea
A D
AD
Mathey-Prevot
B
B
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000502:physiology*; D016185:Receptors, Interleukin-3 / Q000235:genetics; D014162:Transfection
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D016185:Receptors, Interleukin-3; D004921:Erythropoietin; D005914:Globins