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Mol Cell Biol, March 1998, p. 1172-1180, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Erythropoietin and Friend Virus gp55 Activate Different JAK/STAT Pathways through the Erythropoietin Receptor in Erythroid Cells

Yasuko Yamamura,¹ Hisato Senda,^1,2 Yukio Kageyama,³ Tomoko Matsuzaki,¹ Makoto Noda,⁴ and Yoji Ikawa^1,*

Department of Retroviral Regulation, Medical Research Division,¹ and Department of Urology, School of Medicine,³ Tokyo Medical and Dental University, Tokyo 113, Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto 606,⁴ and Central Research Laboratories, Kaken Pharmaceutical Co., Kyoto 607,² Japan

Received 13 August 1997/Returned for modification 28 September 1997/Accepted 1 December 1997

Abnormal erythropoietin (EPO)-independent cell growth is induced after infection of erythroid progenitor cells with a polycythemic strain of Friend virus (FV_p). Binding of its Env-related glycoprotein (gp55) to the EPO receptor (EPOR) mimics the activation of the EPOR with EPO. We investigated the gp55-EPOR signaling in erythroblastoid cells from mice infected with FV_p and in cells of FV_p-induced or gp55-transgenic-mouse-derived erythroleukemia cell lines, comparing it with the EPO-EPOR signaling in EPO-responsive erythroblastoid cells. While the Janus protein tyrosine kinase JAK2 and the transcription factor STAT5 became tyrosine phosphorylated with the EPO stimulation in EPO-responsive erythroblastoid cells from anemic mice, JAK1 and STAT5 were constitutively tyrosine phosphorylated in all of these FV_p gp55-induced erythroblastoid or erythroleukemic cells. Moreover, this constitutively tyrosine-phosphorylated STAT5 was unable to bind to its specific DNA sequences and did not translocate to the nucleus. Nuclear translocation and DNA binding of this STAT5 species required EPO stimulation. These findings clearly indicate that the FV_p gp55-EPOR signaling is distinct from the EPO-EPOR signaling and suggest that STAT5 may not play an essential role in the transmission of the cell growth signals in FV_p gp55-induced erythroleukemia cells.

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^* Corresponding author. Mailing address: Department of Retroviral Regulation, Tokyo Medical and Dental University Medical Research Division, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan. Phone: 81-3-5803-5159. Fax: 81-3-3814-7172. E-mail: y.ikawa.mbch{at}med.tmd.ac.jp.

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