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The Akt1 Isoform Is Required for Optimal IFN-β Transcription through Direct Phosphorylation of β-Catenin
- Source :
- The Journal of Immunology. 189:3104-3111
- Publication Year :
- 2012
- Publisher :
- The American Association of Immunologists, 2012.
-
Abstract
- 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.
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 189
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi...........8b62a06c377a20ee8c717759fb466104