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

ABSTRACT: 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.

SUBMITTER: Hara H

PROVIDER: S-EPMC4813763 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Hara Hideki H Tsuchiya Kohsuke K Kawamura Ikuo I Fang Rendong R Hernandez-Cuellar Eduardo E Shen Yanna Y Mizuguchi Junichiro J Schweighoffer Edina E Tybulewicz Victor V Mitsuyama Masao M

Nature immunology 20131103 12

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 ...[more]

PMID: 24185614

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ASC Speck Formation after Inflammasome Activation in Primary Human Keratinocytes

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| S-EPMC8589508 | biostudies-literature

Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation.

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The Inflammasome Adaptor ASC Induces Procaspase-8 Death Effector Domain Filaments.

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A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly.

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