The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-catenin.
نویسندگان
چکیده
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 Ser(552), 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 Ser(552). Taken together, these results demonstrate that the Akt1 isoform is required for β-catenin-mediated promotion of IFN-β transcription downstream of TLR3 activation.
منابع مشابه
The Akt1 Isoform Is Required for Optimal IFN-b Transcription through Direct Phosphorylation of b-Catenin
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ورودعنوان ژورنال:
- Journal of immunology
دوره 189 6 شماره
صفحات -
تاریخ انتشار 2012