Possible Role of Phosphoinositide-3-Kinase in Mx1 Protein Translation and Antiviral Activity of Interferon-Omega-Stimulated HeLa Cells
| Autor: | Ki-Dae Park, Young-Jun Seo, Il-Ung Oh, Seunghwa Hong, Mi-Hee Kim, Sue-Nie Park, Seungtae Chung, Minjoung Choi, Hong-Won Suh, Sun Hee Kim |
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| Rok vydání: | 2011 |
| Předmět: |
Myxovirus Resistance Proteins
Blotting Western Cell Culture Techniques Mitogen-activated protein kinase kinase Antiviral Agents Phosphatidylinositol 3-Kinases Cytopathogenic Effect Viral GTP-Binding Proteins Chlorocebus aethiops Animals Humans ASK1 Encephalomyocarditis virus Protein kinase A Vero Cells Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Pharmacology Phosphoinositide 3-kinase MAP kinase kinase kinase biology Akt/PKB signaling pathway Chemistry Vesiculovirus General Medicine Cell biology Protein Biosynthesis Interferon Type I biology.protein HeLa Cells |
| Zdroj: | Pharmacology. 87:224-231 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Interferon ω (IFN-ω), a cytokine released during innate immune activation, is well known for promoting direct antiviral responses; however, the possible signal pathways that are initiated by IFN-ω binding to the type I IFN receptors have not been fully studied. Here, we provide evidence that activation of phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling plays a pivotal role in the generation of IFN-ω-mediated biological responses. We found that LY294002 (PI3K inhibitor)-attenuated antiviral activities are induced by IFN-ω treatment. Although such effects of LY294002 are unrelated to regulatory activities on IFN-ω-dependent Mx1 (myxovirus resistance 1) or Mx2 gene transcriptional regulation, translation of Mx1 protein, which was known as a key mediator of cell-autonomous antiviral resistance, was significantly reduced by PI3K inhibition. Further studies showed that PI3K inhibition using LY294002 leads to a decrease in PI3K substrate Akt and mitogen-activated protein kinase extracellular signal-regulated kinase and p38 phosphorylation/activation. In addition, although LY294002 was not able to reduce STAT1 activation, we found that the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway was significantly attenuated by inhibition of the PI3K/Akt signaling pathway. These results indicate that the PI3K/Akt pathway is a common and central integrator for antiviral responses in IFN-ω signaling via its regulatory effects on mTOR that are required for initiation of mRNA translation of Mx genes. |
| Databáze: | OpenAIRE |
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