Title
| 1. | Identification of a novel in vivo virus-targeted phosphorylation site in interferon regulatory factor-3 (IRF3). |
Abstract
| 2. | The transcription factor interferon regulatory factor-3 (IRF3) regulates expression of type I interferon-beta and plays an important role in antiviral immunity. |
| 3. | Despite the biological importance of IRF3, its in vivo phosphorylation pattern has not been reported. |
| 4. | In this study, we have identified residues in IRF3 that are phosphorylated in vivo after infection with Sendai virus. |
| 5. | We found that Sendai virus induced phosphorylation of the C-terminal residues Thr(390) and Ser(396), in addition to either Ser(385) or Ser(386). |
| 6. | Moreover, Ser(173) and Ser(175) were constitutively phosphorylated. |
| 7. | Ser(396) has previously been suggested to be the major target of the IRF3-activating kinase TBK1 (TANK-binding kinase-1), whereas Thr(390) has not previously been implicated in IRF3 regulation. |
| 8. | Mutagenesis studies indicated that phosphorylation of Thr(390) promotes Ser(396) phosphorylation and binding to the coactivator cAMP-response element-binding protein. |
| 9. | Taken together, our results show that IRF3 is subject to multiple interdependent phosphorylations, and we identify Thr(390) as a novel in vivo phosphorylation site that modulates the phosphorylation status of TBK1-targeted Ser(396). |
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