Constitutive activation of Stat-related DNA-binding proteins in erythroid cells by the Friend spleen focus-forming virus.
The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of the erythroid hormone erythropoietin (Epo). In an attempt to understand how the virus alters the growth of erythroid cells, studies were carried out to determine if virus infection leads to the constitutive activation of the Jak-Stat pathway, one of the signal transduction pathways activated by Epo. Our data indicates that expression of SFFV in erythroid cells leads to the constitutive activation of the same Stat proteins that are transiently activated by Epo. While constitutive activation of Stat proteins by SFFV is associated with Epo-independent proliferation of splenic erythroid progenitor cells from Fv-2-sensitive mice and Epo-dependent HCD-57 cells, it is not sufficient to induce their differentiation. Although constitutive activation of the same Stat proteins is detected in erythroid cells from SFFV-infected Fv-2-resistant mice, it does not lead to their Epo-independent growth. It is also not required for transformation of erythroid cells by SFFV. Studies are in progress to identify the mechanism by which Stat proteins are phosphorylated in SFFV-infected cells in the absence of Epo. Although it has been shown that Epo activates Stat proteins through Jak2 kinase, our results suggest that the SFFV-induced Stat protein activation is Jak2-independent.
Ohashi
T
T
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702-1201, USA.
Masuda
M
M
Ruscetti
S K
SK
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology; D016762:Genes, fos; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000821:virology; D004915:Leukemia, Erythroblastic, Acute / Q000503:physiopathology* / Q000821:virology; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013155:Spleen Focus-Forming Viruses / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects
D004268:DNA-Binding Proteins; D004921:Erythropoietin; D011494:Protein Kinases