| First Author | Qu F | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 19 | Pages | 3925-37 |
| PubMed ID | 22851696 | Mgi Jnum | J:189138 |
| Mgi Id | MGI:5444536 | Doi | 10.1128/MCB.00268-12 |
| Citation | Qu F, et al. (2012) TRAF6-dependent Act1 phosphorylation by the IkappaB kinase-related kinases suppresses interleukin-17-induced NF-kappaB activation. Mol Cell Biol 32(19):3925-37 |
| abstractText | Interleukin-17 (IL-17) is critically involved in the pathogenesis of various inflammatory disorders. IL-17 receptor (IL-17R)-proximal signaling complex (IL-17R-Act1-TRAF6) is essential for IL-17-mediated NF-kappaB activation, while IL-17-mediated mRNA stability is TRAF6 independent. Recently, inducible IkappaB kinase (IKKi) has been shown to phosphorylate Act1 on Ser 311 to mediate IL-17-induced mRNA stability. Here we show that TANK binding kinase 1 (TBK1), the other IKK-related kinase, directly phosphorylated Act1 on three other Ser sites to suppress IL-17R-mediated NF-kappaB activation. IL-17 stimulation activated TBK1 and induced its association with Act1. IKKi also phosphorylated Act1 on the three serine sites and played a redundant role with TBK1 in suppressing IL-17-induced NF-kappaB activation. Act1 phosphorylation on the three sites inhibited its association with TRAF6 and consequently NF-kappaB activation in IL-17R signaling. Interestingly, TRAF6, but not TRAF3, which is the upstream adaptor of the IKK-related kinases in antiviral signaling, was critical for IL-17-induced Act1 phosphorylation. TRAF6 was essential for IL-17-induced TBK1 activation, its association with Act1, and consequent Act1 phosphorylation. Our findings define a new role for the IKK-related kinases in suppressing IL-17-mediated NF-kappaB activation through TRAF6-dependent Act1 phosphorylation. |
