Fusion of the Erythropoietin Receptor and the Friend Spleen Focus-forming Virus Gp55 Glycoprotein Transforms a Factor-dependent Hematopoietic Cell Line

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Feb 1

PMID 8423798

Citations 9

Authors

M O Showers

J C DeMartino

Y Saito

A D DAndrea

Affiliations

Soon will be listed here.

Abstract

The Friend spleen focus-forming virus (SFFV) gp55 glycoprotein binds to the erythropoietin receptor (EPO-R), causing constitutive receptor signaling and the first stage of Friend erythroleukemia. We have used three independent strategies to further define this transforming molecular interaction. First, using a retroviral selection strategy, we have isolated the cDNAs encoding three fusion polypeptides containing regions of both EPO-R and gp55. These fusion proteins, like full-length gp55, transformed the Ba/F3 factor-dependent hematopoietic cell line and localized the transforming activity of gp55 to its transmembrane domain. Second, we have isolated a mutant of gp55 (F-gp55-M1) which binds, but fails to activate, EPO-R. We have compared the transforming activity of this gp55 mutant with the EPO-R-gp55 fusion proteins and with other variants of gp55, including wild-type polycythemia Friend gp55 and Rauscher gp55. All of the fusion polypeptides and mutant gp55 polypeptides were expressed at comparable levels, and all coimmunoprecipitated with wild-type EPO-R, but only the Friend gp55 and the EPO-R-gp55 fusion proteins constitutively activated wild-type EPO-R. Third, we have examined the specificity of the EPO-R-gp55 interaction by comparing the differential activation of murine and human EPO-R by gp55. Wild-type gp55 had a highly specific interaction with murine EPO-R; gp55 bound, but did not activate, human EPO-R.

Citing Articles

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Activation of the erythropoietin receptor by the gp55-P viral envelope protein is determined by a single amino acid in its transmembrane domain.

Constantinescu S, Liu X, Beyer W, Fallon A, Shekar S, Henis Y EMBO J. 1999; 18(12):3334-47.

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References

Yoshimura A, Longmore G, Lodish H . Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity. Nature. 1990; 348(6302):647-9. DOI: 10.1038/348647a0. View

DAndrea A, Fasman G, Lodish H . Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family. Cell. 1989; 58(6):1023-4. DOI: 10.1016/0092-8674(89)90499-6. View

Hoatlin M, Kozak S, Lilly F, Chakraborti A, Kozak C, Kabat D . Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. Proc Natl Acad Sci U S A. 1990; 87(24):9985-9. PMC: 55299. DOI: 10.1073/pnas.87.24.9985. View

DAndrea A, Yoshimura A, Youssoufian H, Zon L, Koo J, Lodish H . The cytoplasmic region of the erythropoietin receptor contains nonoverlapping positive and negative growth-regulatory domains. Mol Cell Biol. 1991; 11(4):1980-7. PMC: 359883. DOI: 10.1128/mcb.11.4.1980-1987.1991. View

Li J, Baltimore D . Mechanism of leukemogenesis induced by mink cell focus-forming murine leukemia viruses. J Virol. 1991; 65(5):2408-14. PMC: 240593. DOI: 10.1128/JVI.65.5.2408-2414.1991. View

Marchuk D, Drumm M, Saulino A, Collins F . Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products. Nucleic Acids Res. 1991; 19(5):1154. PMC: 333800. DOI: 10.1093/nar/19.5.1154. View

Sitbon M, dAuriol L, Ellerbrok H, Andre C, Nishio J, Perryman S . Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Proc Natl Acad Sci U S A. 1991; 88(13):5932-6. PMC: 51992. DOI: 10.1073/pnas.88.13.5932. View

Casadevall N, Lacombe C, Muller O, Gisselbrecht S, Mayeux P . Multimeric structure of the membrane erythropoietin receptor of murine erythroleukemia cells (Friend cells). Cross-linking of erythropoietin with the spleen focus-forming virus envelope protein. J Biol Chem. 1991; 266(24):16015-20. View

Ben-David Y, Bernstein A . Friend virus-induced erythroleukemia and the multistage nature of cancer. Cell. 1991; 66(5):831-4. DOI: 10.1016/0092-8674(91)90428-2. View

10.

Srinivas R, Kilpatrick D, Tucker S, Rui Z, Compans R . The hydrophobic membrane-spanning sequences of the gp52 glycoprotein are required for the pathogenicity of Friend spleen focus-forming virus. J Virol. 1991; 65(10):5272-80. PMC: 249006. DOI: 10.1128/JVI.65.10.5272-5280.1991. View

11.

Fukunaga R, Pan C, Seto Y, Nagata S . Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J. 1991; 10(10):2855-65. PMC: 452996. DOI: 10.1002/j.1460-2075.1991.tb07835.x. View

12.

Longmore G, Lodish H . An activating mutation in the murine erythropoietin receptor induces erythroleukemia in mice: a cytokine receptor superfamily oncogene. Cell. 1991; 67(6):1089-102. DOI: 10.1016/0092-8674(91)90286-8. View

13.

Daley G, Van Etten R, Jackson P, Bernards A, Baltimore D . Nonmyristoylated Abl proteins transform a factor-dependent hematopoietic cell line. Mol Cell Biol. 1992; 12(4):1864-71. PMC: 369630. DOI: 10.1128/mcb.12.4.1864-1871.1992. View

14.

Majumdar M, Cho C, Fox M, Eckner K, Kozak S, Kabat D . Mutations in the env gene of friend spleen focus-forming virus overcome Fv-2r-mediated resistance to Friend virus-induced erythroleukemia. J Virol. 1992; 66(6):3652-60. PMC: 241148. DOI: 10.1128/JVI.66.6.3652-3660.1992. View

15.

Yoshimura A, Zimmers T, Neumann D, Longmore G, Yoshimura Y, Lodish H . Mutations in the Trp-Ser-X-Trp-Ser motif of the erythropoietin receptor abolish processing, ligand binding, and activation of the receptor. J Biol Chem. 1992; 267(16):11619-25. View

16.

Zon L, Moreau J, Koo J, Mathey-Prevot B, DAndrea A . The erythropoietin receptor transmembrane region is necessary for activation by the Friend spleen focus-forming virus gp55 glycoprotein. Mol Cell Biol. 1992; 12(7):2949-57. PMC: 364508. DOI: 10.1128/mcb.12.7.2949-2957.1992. View

17.

Mount S . A catalogue of splice junction sequences. Nucleic Acids Res. 1982; 10(2):459-72. PMC: 326150. DOI: 10.1093/nar/10.2.459. View

18.

Amanuma H, KATORI A, Obata M, Sagata N, Ikawa Y . Complete nucleotide sequence of the gene for the specific glycoprotein (gp55) of Friend spleen focus-forming virus. Proc Natl Acad Sci U S A. 1983; 80(13):3913-7. PMC: 394169. DOI: 10.1073/pnas.80.13.3913. View

19.

Wolff L, Scolnick E, Ruscetti S . Envelope gene of the Friend spleen focus-forming virus: deletion and insertions in 3' gp70/p15E-encoding region have resulted in unique features in the primary structure of its protein product. Proc Natl Acad Sci U S A. 1983; 80(15):4718-22. PMC: 384115. DOI: 10.1073/pnas.80.15.4718. View

20.

Clark S, Mak T . Complete nucleotide sequence of an infectious clone of Friend spleen focus-forming provirus: gp55 is an envelope fusion glycoprotein. Proc Natl Acad Sci U S A. 1983; 80(16):5037-41. PMC: 384183. DOI: 10.1073/pnas.80.16.5037. View