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. 2015 Mar;16(3):246-57.
doi: 10.1038/ni.3097. Epub 2015 Feb 2.

The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor TRAF6

Shi Jiao  1 , Zhen Zhang  1 , Chuanchuan Li  1 , Min Huang  1 , Zhubing Shi  1 , Yanyan Wang  1 , Xiaomin Song  1 , Heng Liu  1 , Chunyang Li  1 , Min Chen  1 , Wenjia Wang  1 , Yun Zhao  1 , Zhengfan Jiang  2 , Hongyan Wang  1 , Catherine C L Wong  1 , Chen Wang  1 , Zhaocai Zhou  3
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The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor TRAF6

Shi Jiao et al. Nat Immunol. 2015 Mar.

Abstract

Immune responses need to be tightly controlled to avoid excessive inflammation and prevent unwanted host damage. Here we report that germinal center kinase MST4 responded dynamically to bacterial infection and acted as a negative regulator of inflammation. We found that MST4 directly interacted with and phosphorylated the adaptor TRAF6 to prevent its oligomerization and autoubiquitination VSports手机版. Accordingly, MST4 did not inhibit lipopolysaccharide-induced cytokine production in Traf6(-/-) embryonic fibroblasts transfected to express a mutant form of TRAF6 that cannot be phosphorylated at positions 463 and 486 (with substitution of alanine for threonine at those positions). Upon developing septic shock, mice in which MST4 was knocked down showed exacerbated inflammation and reduced survival, whereas heterozygous deletion of Traf6 (Traf6(+/-)) alleviated such deleterious effects. Our findings reveal a mechanism by which TRAF6 is regulated and highlight a role for MST4 in limiting inflammatory responses. .

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