This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, J. P. Articles by Fang, C. Search for Related Content PubMed PubMed Citation Articles by Li, J. P. Articles by Fang, C.

 Previous Article  |  Next Article 

J. Virol., Mar 1995, 1714-1719, Vol 69, No. 3
Copyright © 1995, American Society for Microbiology

Cell surface activation of the erythropoietin receptor by Friend spleen focus-forming virus gp55

JP Li, HO Hu, QT Niu and C Fang
Department of Microbiology, New York University Medical Center, New York 10016.

The leukemogenic membrane glycoprotein gp55, encoded by Friend spleen focus-forming virus (SFFV), induces erythroid cell proliferation through its interaction with the erythropoietin receptor (EPO-R). There are two forms of gp55 in SFFV-infected cells: an intracellular form (more than 95% of the total protein), which is localized within the endoplasmic reticulum (ER) membranes, and a cell surface form (about 3 to 5%). Because both forms of the viral proteins bind to EPO-R, it is not clear whether the viral protein induces mitogenesis intracellularly or at the cell surface. To address this question, we constructed an EPO- R mutant that contained a 6-amino-acid (DEKKMP) C-terminus ER retention signal. Biochemical and functional analyses with this mutant indicated that it was completely retained in the ER and not expressed at the cell surface. Further analysis showed that the mutant, like the wild-type EPO-R, interacted with SFFV gp55. However, this apparent intracellular interaction between the two proteins failed to induce growth factor- independent proliferation of Ba/F3 cells. Furthermore, spontaneous variants of the ER-retained EPO-R selected on the basis of their ability to induce cell proliferation when coexpressed with gp55 were exclusively expressed at the cell surface. Thus, our results support the hypothesis that the mitogenic activation of the EPO-R by gp55 requires the interaction of the two proteins at the cell surface.

This article has been cited by other articles:

• Liu, W., Crocker, E., Constantinescu, S. N., Smith, S. O. (2005). Helix Packing and Orientation in the Transmembrane Dimer of gp55-P of the Spleen Focus Forming Virus. Biophys. J 89: 1194-1202 [Abstract] [Full Text]  
• Nishigaki, K., Thompson, D., Hanson, C., Yugawa, T., Ruscetti, S. (2001). The Envelope Glycoprotein of Friend Spleen Focus-Forming Virus Covalently Interacts with and Constitutively Activates a Truncated Form of the Receptor Tyrosine Kinase Stk. J. Virol. 75: 7893-7903 [Abstract] [Full Text]  
• Ney, P. A., D'Andrea, A. D. (2000). Friend erythroleukemia revisited. Blood 96: 3675-3680 [Full Text]  
• Hsieh, F. F., Barnett, L. A., Green, W. F., Freedman, K., Matushansky, I., Skoultchi, A. I., Kelley, L. L. (2000). Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27Kip1 and inactivation of cdk2 kinase. Blood 96: 2746-2754 [Abstract] [Full Text]  
• Laquerre, S., Anderson, D. B., Stolz, D. B., Glorioso, J. C. (1998). Recombinant Herpes Simplex Virus Type 1 Engineered for Targeted Binding to Erythropoietin Receptor-Bearing Cells. J. Virol. 72: 9683-9697 [Abstract] [Full Text]  
• Gomez-Lucia, E., Zhi, Y., Nabavi, M., Zhang, W., Kabat, D., Hoatlin, M. E. (1998). An Array of Novel Murine Spleen Focus-Forming Viruses That Activate the Erythropoietin Receptor. J. Virol. 72: 3742-3750 [Abstract] [Full Text]  
• Yugawa, T., Amanuma, H. (1998). Sequence Flexibility in the Polytropic env gp70-Derived Region of the Membrane Glycoprotein (gp55) of Friend Spleen Focus-Forming Virus Affects Its Biological Activity. J. Virol. 72: 2272-2279 [Abstract] [Full Text]  
• Constantinescu, S. N., Wu, H., Liu, X., Beyer, W., Fallon, A., Lodish, H. F. (1998). The Anemic Friend Virus gp55 Envelope Protein Induces Erythroid Differentiation in Fetal Liver Colony-Forming Units-Erythroid. Blood 91: 1163-1172 [Abstract] [Full Text]  
• Hoatlin, M. E., Christianson, T. A., Keeble, W. W., Hammond, A. T., Zhi, Y., Heinrich, M. C., Tower, P. A., Bagby Jr, G. C. (1998). The Fanconi Anemia Group C Gene Product Is Located in Both the Nucleus and Cytoplasm of Human Cells. Blood 91: 1418-1425 [Abstract] [Full Text]  
• Tarr, K., Watowich, S. S., Longmore, G. D. (1997). Cell Surface Organization of the Erythropoietin Receptor Complex Differs Depending on its Mode of Activation. J. Biol. Chem. 272: 9099-9107 [Abstract] [Full Text]