Differentiation domains of the erythropoietin receptor.
Ectopic expression of the erythropoietin receptor (Epo-R) in Ba/F3, an interleukin-3 (IL-3)-dependent progenitor cell line, confers both Epo-dependent cell growth and Epo-dependent induction of beta-globin mRNA. We have used this system of limited erythroid differentiation to characterize the role of the Epo-R in differentiation. In particular, we have been interested in identifying a differentiation domain of the Epo-R. We have studied three chimeras encoding regions of the extracellular region of the Epo-R and the intracellular region of the IL-3R beta IL-3. After transfection into Ba/F3 cells, all three chimeras conferred Epo-dependent growth and induced the expression of beta-globin, suggesting that the extracellular region of the Epo-R plays a critical role in differentiation. However, a truncated Epo-R containing only the extracellular region of the Epo-R and a 15 amino acid cytoplasmic tail does not induced beta-globin expression, although it is processed to the cell surface and binds Epo. These experiments show that the extracytoplasmic region of the Epo-R is necessary but not sufficient to induce erythroid-specific differentiation in this system.
Carroll
M
M
Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115.
Mathey-Prevot
B
B
D'Andrea
A
A
D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D015672:Erythroid Precursor Cells / Q000166:cytology; D004921:Erythropoietin / Q000494:pharmacology; D015870:Gene Expression; D005914:Globins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017467:Receptors, Erythropoietin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000097:blood; D014162:Transfection
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D014157:Transcription Factors; D004921:Erythropoietin; D005914:Globins