Figure 7
Model for Pyk2-dependent NLRP3 inflammasome activation.
Based on our present results, we propose that: (1) in the absence of NLRP3 stimulus, p-Pyk2 (Tyr402) acts downstream of Syk signaling to phosphorylate CARD of ASC at Tyr146 in the cytoplasm and that bring ASC into an oligomerization-competent state; (2) in the presence of NLRP3 stimulus, NLRP3 oligomers recruit ASC molecules, trigger ASC oligomerization, and then form dense ASC speck by the cross-linking of ASC filament. The CARD of ASC is critical for the cross-linking and mediates the assembly of dense ASC speck, caspase-1 activation, and consequently activates NLRP3 inflammasome; and (3) expression of ASC Y146 mutant significantly abolishes ASC phosphorylation, ASC oligomerization, the cross-linking of ASC filaments to form dense ASC speck, and inflammasome formation.
