Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia

Ji Zhang, Mindy S. Randall, Melanie R. Loyd, Weimin Li, Rachel L. Schweers, Derek A. Persons, Jerold E. Rehg, Constance T. Noguchi, James N. Ihle, Paul A. Ney

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Friend virus is an acutely oncogenic retrovirus that causes erythroblastosis and polycythemia in mice. Previous studies suggested that the Friend virus oncoprotein, gp55, constitutively activates the erythropoietin receptor (EPOR), causing uncontrolled erythroid proliferation. Those studies showed that gp55 confers growth factor independence on an interleukin-3 (IL-3)-dependent cell line (Ba/F3) when the EPOR is coexpressed. Subsequently, we showed that a truncated form of the stem-cell kinase receptor (sf-STK) is required for susceptibility to Friend disease. Given the requirement for sf-STK, we sought to establish the in vivo significance of gp55-mediated activation of the EPOR. We found that the cytoplasmic tyrosine residues of the EPOR, and signal transducer and activator of transcription-5 (STAT5), which acts through these sites, are not required for Friend virus-induced erythroblastosis. The EPOR itself was required for the development of erythroblastosis but not for gp55-mediated erythroid proliferation. Interestingly, the murine EPOR, which is required for gp55-mediated Ba/F3-cell proliferation, was dispensable for erythroblastosis in vivo. Finally, gp55-mediated activation of the EPOR and STAT5 are required for Friend virus-induced polycythemia. These results suggest that Friend virus activates both sf-STK and the EPOR to cause deregulated erythroid proliferation and differentiation.

Original languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalBlood
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

Fingerprint

Friend murine leukemia virus
Erythropoietin Receptors
Polycythemia
Viruses
STAT5 Transcription Factor
Chemical activation
Interleukin-3
Oncogene Proteins
Cell proliferation
Retroviridae
Stem cells
Tyrosine
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Stem Cells
Cells
Cell Proliferation
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Zhang, J., Randall, M. S., Loyd, M. R., Li, W., Schweers, R. L., Persons, D. A., ... Ney, P. A. (2006). Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia. Blood, 107(1), 73-78. https://doi.org/10.1182/blood-2005-05-1784

Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia. / Zhang, Ji; Randall, Mindy S.; Loyd, Melanie R.; Li, Weimin; Schweers, Rachel L.; Persons, Derek A.; Rehg, Jerold E.; Noguchi, Constance T.; Ihle, James N.; Ney, Paul A.

In: Blood, Vol. 107, No. 1, 01.01.2006, p. 73-78.

Research output: Contribution to journalArticle

Zhang, J, Randall, MS, Loyd, MR, Li, W, Schweers, RL, Persons, DA, Rehg, JE, Noguchi, CT, Ihle, JN & Ney, PA 2006, 'Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia', Blood, vol. 107, no. 1, pp. 73-78. https://doi.org/10.1182/blood-2005-05-1784
Zhang, Ji ; Randall, Mindy S. ; Loyd, Melanie R. ; Li, Weimin ; Schweers, Rachel L. ; Persons, Derek A. ; Rehg, Jerold E. ; Noguchi, Constance T. ; Ihle, James N. ; Ney, Paul A. / Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia. In: Blood. 2006 ; Vol. 107, No. 1. pp. 73-78.
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