Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity

被引：301

作者：

Hara, Hideki ^{[1
]}

Tsuchiya, Kohsuke ^{[1
]}

Kawamura, Ikuo ^{[1
]}

Fang, Rendong ^{[1
]}

Hernandez-Cuellar, Eduardo ^{[1
]}

Shen, Yanna ^{[1
,2
]}

Mizuguchi, Junichiro ^{[3
,4
]}

Schweighoffer, Edina ^{[5
]}

Tybulewicz, Victor ^{[5
]}

Mitsuyama, Masao ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Microbiol, Kyoto, Japan

[2] Tianjin Med Univ, Sch Lab Med, Tianjin, Peoples R China

[3] Tokyo Med Univ, Dept Immunol, Tokyo 1608402, Japan

[4] Tokyo Med Univ, Intractable Immunol Res Ctr, Tokyo 1608402, Japan

[5] Natl Inst Med Res, MRC, London NW7 1AA, England

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 12期

基金：

英国医学研究理事会; 日本学术振兴会;

关键词：

CASPASE-1; ACTIVATION; NLRP3; INFLAMMASOME; LISTERIA-MONOCYTOGENES; AIM2; PROTEIN; KINASE; DEATH; INTERLEUKIN-1; MACROPHAGES; IL-1-BETA;

D O I：

10.1038/ni.2749

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The inflammasome adaptor ASC contributes to innate immunity through the activation of caspase-1. Here we found that signaling pathways dependent on the kinases Syk and Jnk were required for the activation of caspase-1 via the ASC-dependent inflammasomes NLRP3 and AIM2. Inhibition of Syk or Jnk abolished the formation of ASC specks without affecting the interaction of ASC with NLRP3. ASC was phosphorylated during inflammasome activation in a Syk-and Jnk-dependent manner, which suggested that Syk and Jnk are upstream of ASC phosphorylation. Moreover, phosphorylation of Tyr144 in mouse ASC was critical for speck formation and caspase-1 activation. Our results suggest that phosphorylation of ASC controls inflammasome activity through the formation of ASC specks.

引用

页码：1247 / +

页数：11

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