DYRK3 Dual-specificity Kinase Attenuates Erythropoiesis during Anemia
| Autor: | Arvind Dev, Kim Rance, Estelle Houde, Haydn M. Prosser, Evelyn Grau, Vinit Karur, Olga Bogacheva, Madhu P. Menon, Elizabeth I. Valoret, Susan J. Pickering, George P. Livi, Oleg Bogachev, Connie L. Erickson-Miller, Don M. Wojchowski, Caretha L. Creasy |
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| Rok vydání: | 2008 |
| Předmět: |
Hemolytic anemia
medicine.medical_specialty Anemia Mice Transgenic Protein Serine-Threonine Kinases Biology Biochemistry Cell Line Mice Molecular Basis of Cell and Developmental Biology Reticulocyte Antigens CD Erythroblast hemic and lymphatic diseases Internal medicine Receptors Transferrin medicine Animals Humans Erythropoiesis Transgenes Progenitor cell Molecular Biology Alleles Bone Marrow Transplantation Mice Knockout Cell Biology Protein-Tyrosine Kinases medicine.disease Erythropoietin receptor Endocrinology medicine.anatomical_structure Erythropoietin Cancer research Fluorouracil K562 Cells medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 283:36665-36675 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m807844200 |
| Popis: | During anemia erythropoiesis is bolstered by several factors including KIT ligand, oncostatin-M, glucocorticoids, and erythropoietin. Less is understood concerning factors that limit this process. Experiments performed using dual-specificity tyrosine-regulated kinase-3 (DYRK3) knock-out and transgenic mice reveal that erythropoiesis is attenuated selectively during anemia. DYRK3 is restricted to erythroid progenitor cells and testes. DYRK3-/- mice exhibited essentially normal hematological profiles at steady state and reproduced normally. In response to hemolytic anemia, however, reticulocyte production increased severalfold due to DYRK3 deficiency. During 5-fluorouracil-induced anemia, both reticulocyte and red cell formation in DYRK3-/- mice were elevated. In short term transplant experiments, DYRK3-/- progenitors also supported enhanced erythroblast formation, and erythropoietic advantages due to DYRK3-deficiency also were observed in 5-fluorouracil-treated mice expressing a compromised erythropoietin receptor EPOR-HM allele. As analyzed ex vivo, DYRK3-/- erythroblasts exhibited enhanced CD71posTer119pos cell formation and 3HdT incorporation. Transgenic pA2gata1-DYRK3 mice, in contrast, produced fewer reticulocytes during hemolytic anemia, and pA2gata1-DYRK3 progenitors were compromised in late pro-erythroblast formation ex vivo. Finally, as studied in erythroid K562 cells, DYRK3 proved to effectively inhibit NFAT (nuclear factor of activated T cells) transcriptional response pathways and to co-immunoprecipitate with NFATc3. Findings indicate that DYRK3 attenuates (and possibly apportions) red cell production selectively during anemia. |
| Databáze: | OpenAIRE |
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