Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene

Maureen Hoatlin, Susan L. Kozak, Frank Lilly, Anuradha Chakraborti, Christine A. Kozak, David Kabat

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Abstract

The leukemogenic membrane glycoprotein (gp55) encoded by Friend spleen focus-forming virus appears to bind to erythropoietin receptors (EpoR) to stimulate erythroblastosis [Li, J.-P., D'Andrea, A. D., Lodish, H. F. & Baltimore, D. (1990) Nature (London) 343, 762-764]. To directly compare the effects of gp55 with erythropoietin (Epo), we produced retrovirions that encode either gp55, Epo, or EpoR. After infection with EpoR virus, interleukin 3-dependent DA-3 cells bound 125I-labeled Epo and grew without interleukin 3 in the presence of Epo. These latter cells, but not parental DA-3 cells, became factor-independent after superinfection either with Epo virus or with Friend spleen focus-forming virus. In addition, Epo virus caused a disease in mice that mimicked Friend erythroleukemia. Although Fv-2r homozygotes are susceptible to all other retroviral diseases, they are resistant to both Epo viral and Friend viral erythroleukemias. These results indicate that both gp55 and Epo stimulate EpoR and that the Fv-2 gene encodes a protein that controls response to these ligands. However, the Fv-2 protein is not EpoR because the corresponding genes map to opposite ends of mouse chromosome 9. These results have important implications for understanding signal transduction by EpoR and the role of host genetic variation in controlling susceptibility to an oncogenic protein.

Original languageEnglish (US)
Pages (from-to)9985-9989
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number24
Publication statusPublished - 1990

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Keywords

  • Cancer genes
  • Friend virus
  • Leukemia

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. / Hoatlin, Maureen; Kozak, Susan L.; Lilly, Frank; Chakraborti, Anuradha; Kozak, Christine A.; Kabat, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 24, 1990, p. 9985-9989.

Research output: Contribution to journalArticle