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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
RKIP and TBK1 form a positive feedback loop to promote type I interferon production in innate immunity
Meidi Gu1, Zhiyong Liu1, Rongrong Lai1
1Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, China.
Abstract:
TANK-binding kinase 1 (TBK1) activation is a central event in type I interferon production in anti-virus innate immunity. However, the regulatory mechanism underlying TBK1 activation remains unclear. Here we report that Raf kinase inhibitory protein (RKIP) is essential for TBK1 activation and type I interferon production triggered by viral infection. Upon viral infection, RKIP is phosphorylated at serine 109 (S109) by TBK1. Phosphorylation of RKIP enhances its interaction with TBK1 and in turn promotes TBK1 autophosphorylation. Mutation of RKIP S109 to alanine abrogates the interaction between RKIP and TBK1, and the anti-viral function of RKIP RKIP deficiency inhibits intracellular double-stranded RNA- or DNA-induced type I interferon production. Consistently, RKIP deficiency renders the mice more susceptible to vesicular stomatitis virus (VSV) and herpes simplex virus (HSV) infections. This study reveals a previously unrecognized positive feedback loop between RKIP and TBK1 that is essential for type I interferon production in anti-viral innate immunity.
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