The Akt1 Isoform Is Required for Optimal IFN-β Transcription through Direct Phosphorylation of β-Catenin
| العنوان: | The Akt1 Isoform Is Required for Optimal IFN-β Transcription through Direct Phosphorylation of β-Catenin |
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| المؤلفون: | Huali Jin, Richard D. Ye, Nissim Hay, Feng Qian, Bin He, Benjamin N. Gantner |
| المصدر: | The Journal of Immunology. 189:3104-3111 |
| بيانات النشر: | The American Association of Immunologists, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Gene isoform, Proto-Oncogene Proteins c-akt, Kinase, GSK-3, embryonic structures, Immunology, Immunology and Allergy, Phosphorylation, AKT1, Biology, Signal transduction, Molecular biology, Protein kinase B |
| الوصف: | IFN-β is a critical antiviral cytokine that is capable of modulating the systemic immune response. The transcriptional induction of IFN-β is a highly regulated process, involving the activation of pattern recognition receptors and their downstream signaling pathways. The Akt family of serine/threonine kinases includes three isoforms. The specific role for the individual Akt isoforms in pattern recognition and signaling remains unclear. In this article, we report that the TLR3-mediated expression of IFN-β is blunted in cells that lack Akt1. The expression of IFN-β–inducible genes such as CCL5 and CXCL10 was also reduced in Akt1-deficient cells; the induction of TNF-α and CXCL2, whose expression does not rely on IFN-β, was not reduced in the absence of Akt1. Macrophages from Akt1−/− mice displayed deficient clearance of HSV-1 along with reduced IFN-β expression. Our results demonstrate that Akt1 signals through β-catenin by phosphorylation on Ser552, a site that differs from the glycogen synthase kinase 3 β phosphorylation site. Stimulation of a chemically activated version of Akt1, in the absence of other TLR3-dependent signaling, was sufficient for accumulation and phosphorylation of β-catenin at Ser552. Taken together, these results demonstrate that the Akt1 isoform is required for β-catenin–mediated promotion of IFN-β transcription downstream of TLR3 activation. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::8b62a06c377a20ee8c717759fb466104Test https://doi.org/10.4049/jimmunol.1201669Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........8b62a06c377a20ee8c717759fb466104 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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