Temporal regulation of Stat5 activity in determination of cell differentiation program.
Although Stat5 is activated by various cytokines, only erythropoietin (Epo) and a small number of cytokines induce Stat5-dependent erythroid differentiation. Here, by using a reporter gene system to monitor transcriptional activity of Stat5, we showed that Epo but not interleukin (IL)-3 supports sustained activation of Stat5, which induces globin gene expression. IL-3 or IL-2 stimulation inhibits Epo-induced globin gene expression. The acidic region of the IL-2 receptor beta-chain was essential for this inhibition. These results underscore the importance of temporal regulation of Stat activity for regulation of cytokine-specific cell differentiation.
Hoshino
Akemi
A
Department of Pathology, New York University School of Medicine, 550 First Avenue, MSB-126, New York, NY 10016, USA.
Fujii
Hodaka
H
D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology; D004921:Erythropoietin / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic
D007376:Interleukin-2; D007377:Interleukin-3; D050799:STAT5 Transcription Factor; D004921:Erythropoietin