Figure 4.

Regulation of RIPK1 activity through phosphorylation and dephosphorylation. This schematic illustrates the dynamic regulation of RIPK1-dependent cell death pathways. Inhibitory phosphorylation events on RIPK1, catalyzed by multiple kinases, serve as important checkpoints for cell death activation. Following cell death induction, the PPP1R3G/PP1γ holoenzyme is recruited to complex I to remove the inhibitory phosphorylation on RIPK1. This process enables RIPK1 autophosphorylation to activate its kinase activity. Consequently, activated RIPK1 triggers downstream signaling cascades, leading to apoptosis and necroptosis. The balance between inhibitory phosphorylation and PPP1R3G/PP1γ-mediated dephosphorylation serves as a key regulatory mechanism for RIPK1-dependent cell death processes. The red stripes in the diagram of RIPK1 and RIPK3 indicate the RHIM domain.