| First Author | Hemmi H | Year | 2004 |
| Journal | J Exp Med | Volume | 199 |
| Issue | 12 | Pages | 1641-50 |
| PubMed ID | 15210742 | Mgi Jnum | J:91363 |
| Mgi Id | MGI:3046607 | Doi | 10.1084/jem.20040520 |
| Citation | Hemmi H, et al. (2004) The Roles of Two IkappaB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection. J Exp Med 199(12):1641-50 |
| abstractText | Viral infection and stimulation with lipopolysaccharide (LPS) or double stranded RNA (dsRNA) induce phosphorylation of interferon (IFN) regulatory factor (IRF)-3 and its translocation to the nucleus, thereby leading to the IFN-beta gene induction. Recently, two IkappaB kinase (IKK)-related kinases, inducible IkappaB kinase (IKK-i) and TANK-binding kinase 1 (TBK1), were suggested to act as IRF-3 kinases and be involved in IFN-beta production in Toll-like receptor (TLR) signaling and viral infection. In this work, we investigated the physiological roles of these kinases by gene targeting. TBK1-deficient embryonic fibroblasts (EFs) showed dramatic decrease in induction of IFN-beta and IFN-inducible genes in response to LPS or dsRNA as well as after viral infection. However, dsRNA-induced expression of these genes was residually detected in TBK1-deficient cells and intact in IKK-i-deficient cells, but completely abolished in IKK-i/TBK1 doubly deficient cells. IRF-3 activation, in response not only to dsRNA but also to viral infection, was impaired in TBK1-deficient cells. Together, these results demonstrate that TBK1 as well as, albeit to a lesser extent, IKK-i play a crucial role in the induction of IFN-beta and IFN-inducible genes in both TLR-stimulated and virus-infected EFs. |
