Figure 9. Activation of NLRP1 by the ZAKα/P38 signaling pathway.

• A
  Schemes showing the domain organization of human wild type NLRP1 and the S107A and S107D mutants. Phosphorylation of the linker domain by ZAKα (MAP3K)/MAP2K/P38 (MAPK) axis is highlighted. Note that S107A cannot be phosphorylated by P38, while phosphomimetic S107D is constitutively active independently of P38 activation.
• B
  The NLRP1 inflammasome critically regulates hematopoiesis following its activation by ZAKα/P38 signaling pathways, which is initiated by ribosomal stress. Inhibition of this pathway with nilotinib rescues erythropoiesis defects in HSPCs from DBA and neutrophilic inflammation patients.