MECHANISM OF INTERFERON ACTION - IN-VIVO ACTIVATION OF 91 KDA TRANSCRIPTION FACTOR

Interferons are a family of secreted polypeptides with distinct biolog ical effects. These effects include the regulation of expression of sp ecific cellular genes, antiviral properties, and inhibition of cell gr owth and proliferation. We investigated the effect of sodium orthovana date (vanadate), an inhibitor of protein-phosphotyrosine phosphatases, on early biochemical events associated with the stimulation of transc ription factor p91 activation by interferon-alpha (IFN alpha) in live human cells. We report that the treatment of cells with vanadate selec tively potentiated (2-3 fold) the levels of IFN-stimulated tyrosine ph osphorylation of p91 (find not of p113) as compared to the levels of p 91 activated by IFN alone and that this was associated with the increa sed accumulation of phosphorylated p91 in the nucleus, and the activat ion of protein tyrosine kinases that phosphorylate p91. These results suggest the possible involvement of a vanadate sensitive protein-tyros ine phosphatase(s) in the deactivation of phosphorylated p91 in live h uman cells.