The distal region and receptor tyrosines of the Epo receptor are non-essential for in vivo erythropoiesis

Heesuk Zang, Ken Sato, Hideaki Nakajima, Catriona McKay, Paul A. Ney, James N. Ihle

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

The erythropoietin receptor (EpoR) is required for the proliferation and survival of committed erythroid lineage cells. Previous studies have utilized receptor mutations to show the requirement for the distal half of the cytoplasmic domain of the EpoR and receptor tyrosines for activation of signaling pathways potentially critical to Epo function. To extend these studies to in vivo erythropoiesis, we have created two mutant strains of mice. One strain (H) contains a truncation of the distal half of the cytoplasmic domain, while the second strain (HM) contains the same truncation as well as the mutation of the residual tyrosine (Y343) to a phenylalanine. Strikingly, both strains of mice are viable, with only slight alterations in constitutive erythropoiesis or in in vitro assays of red cell lineage function. Challenging H mutant mice with continuous injections of Epo results in an erythrocytosis that is not seen in HM mice. The results demonstrate that neither the distal region nor receptor tyrosines are essential for in vivo EpoR function, but contribute to receptor function in a subtle manner.

Original languageEnglish
Pages (from-to)3156-3166
Number of pages11
JournalEMBO Journal
Volume20
Issue number12
DOIs
Publication statusPublished - 2001 Jun 15
Externally publishedYes

Keywords

  • Cytokine signaling
  • Erythropoiesis
  • Erythropoietin
  • Jak2 kinase
  • Receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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