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 (and 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.
Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.
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Korutla
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Kumar
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053613:Janus Kinase 1; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D019319:Okadaic Acid; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D017027:Protein Tyrosine Phosphatases