| First Author | Gantner BN | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 6 | Pages | 3104-11 |
| PubMed ID | 22904301 | Mgi Jnum | J:189917 |
| Mgi Id | MGI:5447245 | Doi | 10.4049/jimmunol.1201669 |
| Citation | Gantner BN, et al. (2012) The Akt1 isoform is required for optimal IFN-beta transcription through direct phosphorylation of beta-catenin. J Immunol 189(6):3104-11 |
| abstractText | IFN-beta is a critical antiviral cytokine that is capable of modulating the systemic immune response. The transcriptional induction of IFN-beta 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-beta is blunted in cells that lack Akt1. The expression of IFN-beta-inducible genes such as CCL5 and CXCL10 was also reduced in Akt1-deficient cells; the induction of TNF-alpha and CXCL2, whose expression does not rely on IFN-beta, was not reduced in the absence of Akt1. Macrophages from Akt1(-/-) mice displayed deficient clearance of HSV-1 along with reduced IFN-beta expression. Our results demonstrate that Akt1 signals through beta-catenin by phosphorylation on Ser(552), a site that differs from the glycogen synthase kinase 3 beta 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 beta-catenin at Ser(552). Taken together, these results demonstrate that the Akt1 isoform is required for beta-catenin-mediated promotion of IFN-beta transcription downstream of TLR3 activation. |
