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Mechanism of interferon action: in vivo activation of 91 kDa transcription factor
1Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Abstract:
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.
Insights
Sodium orthovanadate enhances interferon-alpha (IFN-α) signaling by boosting p91 phosphorylation. This suggests a role for vanadate-sensitive phosphatases in regulating transcription factor p91 activity in human cells.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Interferons (IFNs) are crucial signaling proteins regulating gene expression, antiviral responses, and cell proliferation.
- Transcription factor p91 activation is a key early event in IFN signaling pathways.
Purpose of the Study:
- To investigate the effect of sodium orthovanadate (vanadate) on interferon-alpha (IFN-α)-induced p91 activation in live human cells.
- To explore the role of protein-phosphotyrosine phosphatases in regulating p91 activity.
Main Methods:
- Treatment of human cells with vanadate and IFN-α.
- Analysis of tyrosine phosphorylation of p91 and p113.
- Assessment of p91 nuclear accumulation and protein tyrosine kinase activity.
Main Results:
- Vanadate treatment potentiated IFN-α-stimulated tyrosine phosphorylation of p91 by 2-3 fold.
- Increased accumulation of phosphorylated p91 was observed in the nucleus.
- Activation of protein tyrosine kinases responsible for p91 phosphorylation was enhanced.
Conclusions:
- Vanadate selectively enhances IFN-α-induced p91 activation.
- These findings suggest the involvement of vanadate-sensitive protein-tyrosine phosphatases in the deactivation of phosphorylated p91.
- A potential regulatory mechanism for p91 activity in human cells is proposed.