Interleukin-3 (IL-3) Inhibits Erythropoietin-induced Differentiation in Ba/F3 Cells via the IL-3 Receptor α Subunit
| Autor: | R K Humphries, Jana Krosl, Gerald Krystal, Jacqueline E. Damen |
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| Rok vydání: | 1996 |
| Předmět: |
Transcription
Genetic Macromolecular Substances Recombinant Fusion Proteins Genetic Vectors Biology Transfection Biochemistry Cell Line Mice hemic and lymphatic diseases Receptors Erythropoietin medicine Animals RNA Messenger Receptor Erythropoietin Molecular Biology Interleukin 3 G alpha subunit food and beverages Cell Differentiation Cell Biology Hematopoietic Stem Cells Molecular biology Receptors Interleukin-3 Clone Cells Globins Erythropoietin receptor Cell biology Kinetics Retroviridae Cell culture embryonic structures Mutagenesis Site-Directed Interleukin-3 Cell Division Intracellular medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 271:27432-27437 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.44.27432 |
| Popis: | Introduction of erythropoietin receptors (EpoRs) into the interleukin-3 (IL-3)-dependent murine hemopoietic cell line, Ba/F3, enables these cells to not only proliferate, after an initial lag in G1, but also to increase beta-globin mRNA levels in response to erythropoietin (Epo). With IL-3 and Epo costimulation, IL-3-induced signaling appears to be dominant since no increase in beta-globin mRNA occurs. Differentiation and proliferation signals may be uncoupled since EpoRs lacking all eight intracellular tyrosines were compromised in proliferative signaling but retained erythroid differentiation ability. Intriguingly, a chimeric receptor of the extracellular domain of the EpoR and the transmembrane and intracellular domains of IL-3RbetaIL-3 chain (EpoR/IL-3RbetaIL-3) was capable of Epo-induced proliferative and differentiating signaling, suggesting either the existence of a second EpoR subunit responsible for differentiation or that the alpha subunit of the IL-3 receptor (IL-3R) prevents it. Arguing against the former, a truncated EpoR lacking an intracellular domain was incapable of promoting proliferation or differentiation. An EpoR/IL-3Ralpha chimera, in contrast, was capable of transmitting a weak Epo-induced proliferative signal but failed to stimulate accumulation of beta-globin mRNA. Most significantly, coexpression of the EpoR/IL-3Ralpha chimera with either EpoR/IL-3Rbeta or wild-type EpoRs suppressed Epo-induced beta-globin mRNA accumulation. Taken together, these results suggest an active role for the IL-3Ralpha subunit in inhibiting EpoR-specific differentiating signals. |
| Databáze: | OpenAIRE |
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