Mechanism of interferon action: In vivo activation of 91 kDa transcription factor

Interferons are a family of secreted polypeptides with distinct biological effects. These effects include the regulation of expression of specific cellular genes, antiviral properties, and inhibition of cell growth and proliferation. We investigated the effect of sodium orthovanadate (vanadate), an inhibitor of protein-phosphotyrosine phosphatases, on early biochemical events associated with the stimulation of transcription factor p91 activation by interferon-alpha (IFN alpha) in live human cells. We report that the treatment of cells with vanadate selectively potentiated (2-3 fold) the levels of IFN-stimulated tyrosine phosphorylation of p91 (find not of p113) as compared to the levels of p91 activated by IFN alone and that this was associated with the increased accumulation of phosphorylated p91 in the nucleus, and the activation of protein tyrosine kinases that phosphorylate p91. These results suggest the possible involvement of a vanadate sensitive protein-tyrosine phosphatase(s) in the deactivation of phosphorylated p91 in live human cells.