Erythropoietin Receptors That Signal Through Stat5 or Stat3 Support Fetal Liver and Adult Erythropoiesis: Lack of Specificity of Stat Signals During Red Blood Cell Development
| Autor: | Ruth A. Busche, Stephanie S. Watowich, Xiaoling Xie, Pamela N. Pharr, Aki Mikami, Gregory D. Longmore |
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| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
STAT3 Transcription Factor
Immunology Biology stat Article Cell Line Colony-Forming Units Assay Mice Fetus Virology hemic and lymphatic diseases medicine Receptors Erythropoietin STAT5 Transcription Factor Animals Erythropoiesis STAT3 STAT5 food and beverages Cell Biology Glycoprotein 130 Milk Proteins Molecular biology Cell biology Erythropoietin receptor DNA-Binding Proteins Liver Erythropoietin embryonic structures biology.protein Trans-Activators Signal transduction medicine.drug Signal Transduction |
| Popis: | Erythropoietin (Epo) is essential for formation of mature red blood cells (RBC). However, the function of Epo receptor (EpoR)-dependent signaling pathways in the regulation of erythropoiesis remains unclear. To determine whether specific Stat signals are required for RBC development, we changed the Stat signaling specificity of the EpoR. The wild-type EpoR activates only Stat5. Thus, we substituted the major Stat5 binding sites (residues 343 and 401) in the EpoR cytoplasmic region with the Stat3 binding/activation motif from gp130. We demonstrated that activated EpoRs containing a single substitution stimulate Stat5 and Stat3, whereas an EpoR with both substitutions stimulates Stat3 but not Stat5. We then determined the ability of these receptors to support fetal liver and adult erythropoiesis. Our results show that erythropoiesis is stimulated by EpoRs that activate Stat5, both Stat5 and Stat3, or Stat3 in place of Stat5. These findings demonstrate that the specificity of EpoR Stat signaling is not essential for RBC development. |
| Databáze: | OpenAIRE |
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