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

Research output: Contribution to journalArticle

68 Citations (Scopus)

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
StatePublished - 1990

Fingerprint

Erythropoietin Receptors
Erythropoietin
Genes
Spleen Focus-Forming Viruses
Leukemia, Erythroblastic, Acute
Interleukin-3
Viruses
Superinfection
Baltimore
Chromosomes, Human, Pair 9
Proteins
Membrane Glycoproteins
Homozygote
Signal Transduction
Ligands

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

@article{cc63023cb0bd4ab6b6da2d40d0748571,
title = "Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene",
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.",
keywords = "Cancer genes, Friend virus, Leukemia",
author = "Maureen Hoatlin and Kozak, {Susan L.} and Frank Lilly and Anuradha Chakraborti and Kozak, {Christine A.} and David Kabat",
year = "1990",
language = "English (US)",
volume = "87",
pages = "9985--9989",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "24",

}

TY - JOUR

T1 - Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene

AU - Hoatlin, Maureen

AU - Kozak, Susan L.

AU - Lilly, Frank

AU - Chakraborti, Anuradha

AU - Kozak, Christine A.

AU - Kabat, David

PY - 1990

Y1 - 1990

N2 - 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.

AB - 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.

KW - Cancer genes

KW - Friend virus

KW - Leukemia

UR - http://www.scopus.com/inward/record.url?scp=0025630450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025630450&partnerID=8YFLogxK

M3 - Article

C2 - 2175917

AN - SCOPUS:0025630450

VL - 87

SP - 9985

EP - 9989

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 24

ER -