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Blood, 1 January 2006, Vol. 107, No. 1, pp. 73-78. Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-05-1784. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-05-1784v1 107/1/73    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Ney, P. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Ney, P. A. Related Collections Hematopoiesis and Stem Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS 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, and Paul A. Ney From the Departments of Biochemistry, Experimental Hematology, and Pathology, St Jude Children's Research Hospital, Memphis, TN; Integrated Program in Biomedical Science, University of Tennessee Health Science Center, Memphis; and the Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The erythropoietin receptor lends a Friendly hand Richard A. Van Etten Blood 2006 107: 5-6. [Full Text] [PDF] This article has been cited by other articles: A. Subramanian, S. Hegde, P. Porayette, M. Yon, P. Hankey, and R. F. Paulson Friend Virus Utilizes the BMP4-Dependent Stress Erythropoiesis Pathway To Induce Erythroleukemia J. Virol., January 1, 2008; 82(1): 382 - 393. [Abstract] [Full Text] [PDF] S. Ni, C. Zhao, G.-S. Feng, R. F. Paulson, and P. H. Correll A Novel Stat3 Binding Motif in Gab2 Mediates Transformation of Primary Hematopoietic Cells by the Stk/Ron Receptor Tyrosine Kinase in Response to Friend Virus Infection Mol. Cell. Biol., May 15, 2007; 27(10): 3708 - 3715. [Abstract] [Full Text] [PDF] M. Rodenburg, M. Fischer, A. Engelmann, S. O. Harbers, M. Ziegler, J. Lohler, and C. Stocking Importance of Receptor Usage, Fli1 Activation, and Mouse Strain for the Stem Cell Specificity of 10A1 Murine Leukemia Virus Leukemogenicity J. Virol., January 15, 2007; 81(2): 732 - 742. [Abstract] [Full Text] [PDF]

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