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

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.