ERYTHROPOIETIN AND FRIEND-VIRUS GP55 ACTIVATE DIFFERENT JAK STAT PATHWAYS THROUGH THE ERYTHROPOIETIN RECEPTOR IN ERYTHROID-CELLS/

Abnormal erythropoietin (EPO)-independent cell growth is induced after infection of erythroid progenitor cells with a polycythemic strain of Friend virus (FVp). Binding of its Env-related glycoprotein (gp55) to the EPO receptor (EPOR) mimics the activation of the EPOR with EPO. W e investigated the gp55-EPOR signaling in erythroblastoid cells from m ice infected with FVp and in cells of FVp-induced or gp55-transgenic-m ouse-derived erythroleukemia cell lines, comparing it with the EPO-EPO R signaling in EPO-responsive erythroblastoid cells. While the janus p rotein tyrosine kinase JAK2 and the transcription factor STAT5 became tyrosine phosphorylated with the EPO stimulation in EPO-responsive ery throblastoid cells from anemic mice, JAK1 and STAT5 were constitutivel y tyrosine phosphorylated in all of these FVp gp55-induced erythroblas toid 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 FVp gp55-EPQR signaling is distinct from th e EPO-EPOR signaling and suggest that STAT5 may not play an essential role in the transmission of the cell growth signals in FVp gp55-induce d erythroleukemia cells.