Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity.
Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity.
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接头 ASC 的磷酸化充当分子开关，控制斑点状聚集体的形成和炎症小体活性。
DOI：
10.1038/ni.2749
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发表时间：
2013-12
影响因子：
30.5
通讯作者：
Mitsuyama M
中科院分区：
文献类型：
--
作者：
Hara H;Tsuchiya K;Kawamura I;Fang R;Hernandez-Cuellar E;Shen Y;Mizuguchi J;Schweighoffer E;Tybulewicz V;Mitsuyama M
炎性小体接头 ASC 通过激活 caspase-1 促进先天免疫。在这里，我们表明 Syk 和 JNK 依赖性信号通路是通过 ASC 依赖性炎症小体 NLRP3 和 AIM2 激活 caspase-1 所必需的。 Syk 或 JNK 的抑制消除了 ASC 斑点的形成，而不影响 ASC 与 NLRP3 的相互作用。 ASC 在炎症小体激活过程中以 Syk 和 JNK 依赖性方式磷酸化，表明 Syk 和 JNK 是 ASC 磷酸化的上游。此外，小鼠 ASC 中 Tyr144 残基的磷酸化对于斑点形成和 caspase-1 激活至关重要。这些结果表明 ASC 的磷酸化通过 ASC 斑点的形成来控制炎症小体活性。
The inflammasome adaptor ASC contributes to innate immunity through the activation of caspase-1. Here we show that Syk and JNK-dependent signaling pathways are required for caspase-1 activation via the ASC-dependent inflammasomes NLRP3 and AIM2. Inhibition of Syk or JNK abolished the formation of ASC specks without affecting interaction of ASC with NLRP3. ASC was phosphorylated during inflammasome activation in a Syk- and JNK-dependent manner, suggesting that Syk and JNK are upstream of ASC phosphorylation. Moreover, phosphorylation of Tyr144 residue in mouse ASC was critical for speck formation and caspase-1 activation. These results suggested that phosphorylation of ASC controls inflammasome activity through ASC speck formation.