Role of STAT5 in interferon-alpha signal transduction in Ba/F3 cells.

In interferon-alpha (IFN-alpha) signalling, the essential role of the transcription factors STAT1 and STAT2 is well established. In contrast, the involvement of other STAT proteins, including STAT5, is much less well understood. Here we show that, in IFN-alpha-responsive Ba/F3 cells, this cytokine stimulates the DNA-binding of STAT5A and B but that IL-3 is a much more potent activator of both STAT5 isoforms. A stably expressed dominant-negative mutant of JAK2 suppressed the IL-3- but not the IFN-alpha-dependent DNA binding of STAT5, suggesting independent mechanisms of its activation. Northern blots revealed that IL-3 strongly induced the expression of two STAT5-regulated genes, pim-1 and oncostatin-M, whereas IFN-alpha had a weak stimulatory effect on pim-1 expression only. In summary our results suggest that, despite the capability of IFN-alpha to stimulate DNA binding of STAT5, this transcription factor does not play a pivotal role in IFN-alpha signalling in Ba/F3 cells.