Divergent cytokine receptors support terminal red blood cell differentiation in vtvo

Aki Mikami, Yun You, Kathleen D. Liu, Liza Thomas, Gregory D. Longmore', H. Ralph

Research output: Contribution to journalArticle

Abstract

Erythropoietin (Epo) is required for red blood cell development; however, it has been difficult to determine experimentally whether the role is instructive or supportive. Chimeric receptors were constructed by replacing the cytoplasmic tail of a constitutively active erythropoietin receptor (cEpoR) with tails of other cytokine receptors. The extracellular domain of cEpoR contains an R129C point substitution that causes constitutive, covalent receptor homodimerization and continuous transmission of signals in the absence of Epo. Through retroviral transduction these ligand-independent activated chimeric receptors were expressed in primary erythroid progenitors in culture and in vivo. Chimeric receptors with cytoplasmic tails from the granulocyte colony stimulating factor receptor or from the growth hormone receptor supported erythroid colony development. A chimeric receptor with a c-mpl tail was partially active. Infection of NIHSwiss mice with these recombinant viruses in the presence of replication competent Rauscher helper virus caused splenomegaly and elevation in hernatocrit. Therefore, EpoR specific signals are not required for the differentiation of erythrocytes. Rather, cytokine-dependent signaling provides a supportive function for erythroid differentiation.

Original languageEnglish
Number of pages1
JournalExperimental Hematology
Volume26
Issue number8
StatePublished - Dec 1 1998
Externally publishedYes

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