Nigericin-Triggered Phosphodynamics in Inflammasome Formation and Pyroptosis

Innate immune signaling relies on phosphorylation cascades for effective responses. While TLR4 stimulation has been well-studied, research on signaling after inflammasome triggers like nigericin is limited. We performed time-resolved phosphoproteomic profiling to explore kinase signaling downstream of nigericin and discovered rapid changes in phosphorylation, particularly involving immune and MAPK pathways. Notably, we identified fluxes in PKC signaling and calcium-responsive proteins, along with phospho-modified metabolic pathways, indicating a role in immunometabolic regulation. Additionally, significant changes in DNA reorganization and damage response proteins linked to pyknosis were observed. Temporal clustering of phospho-dynamics revealed new shifts in signaling cascades after nigericin treatment, underscoring changes in cellular behavior related to inflammatory events