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The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-catenin. J Immunol 2012 Sep 15;189(6):3104-11

Date

08/21/2012

Pubmed ID

22904301

Pubmed Central ID

PMC3658160

DOI

10.4049/jimmunol.1201669

Scopus ID

2-s2.0-84866179288   19 Citations

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 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.

Author List

Gantner BN, Jin H, Qian F, Hay N, He B, Ye RD

Author

Benjamin N. Gantner PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Humans
Interferon-beta
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphorylation
Protein Isoforms
Proto-Oncogene Proteins c-akt
Signal Transduction
Toll-Like Receptor 3
Transcription, Genetic
beta Catenin
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a