Fig. 9
Activation of NLRP1 by the ZAK?/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 ZAK? (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 ZAK?/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. |