Absence of Cytokine Receptor-Dependent Specificity in Red Blood Cell Differentiation in vivo

Erythropoietin (EPO) is required for red blood cell development, but whether EPO-specific signals directly instruct erythroid differentiation is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenitors in mice. Chimeric...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-06, Vol.95 (12), p.7006-7011
Main Authors: Goldsmith, Mark A., Mikami, Aki, You, Yun, Liu, Kathleen D., Thomas, Liza, Pharr, Pamela, Longmore, Gregory D.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Antiserum
Biological Sciences
Blood
Cell Differentiation - physiology
Cell lines
Cellular biology
Cytokine receptors
Developmental biology
Epics
Erythrocytes
Erythrocytes - cytology
Erythrocytes - physiology
Erythroid progenitor cells
Erythropoiesis - physiology
Erythropoietin - physiology
Mice
Progenitor cells
Receptors
Receptors, Erythropoietin - physiology
Recombinant Fusion Proteins - physiology
Rodents
Signal Transduction
Transfection
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Summary:Erythropoietin (EPO) is required for red blood cell development, but whether EPO-specific signals directly instruct erythroid differentiation is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenitors in mice. Chimeric receptors were constructed by replacing the cytoplasmic tail of constitutively active variants of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to granulocyte or platelet production supported complete erythroid development in vitro and in vivo, as did the growth hormone receptor, a nonhematopoietic receptor. Therefore, EPOR-specific signals are not required for terminal differentiation of erythrocytes. Furthermore, we found that cellular context can influence cytokine receptor signaling.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.12.7006