Send to:

Choose Destination
See comment in PubMed Commons below
J Immunol. 2012 Sep 15;189(6):3104-11. doi: 10.4049/jimmunol.1201669. Epub 2012 Aug 17.

The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-catenin.

Author information

  • 1Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.


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.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk