The intracellular signaling pathway by which TNF induces its pleiotropic actions is well-characterized and includes unique components, as well as modules shared with other signaling pathways. TMEM9B as an important component of TNF signaling and which is a module shared with the IL-1beta and Toll-like receptor (TLR) pathways. is a glycosylated protein localized in membranes of the lysosome and partially in early endosomes. The expression of TMEM9B is required for the production of proinflammatory cytokines induced by TNF, IL-1beta, and TLR ligands, but not for apoptotic cell death triggered by TNF or Fas ligand. TMEM9B is essential in TNF activation of both the NF-kappaB and MAPK pathways.TMEM9B is a key component of inflammatory signaling pathways and suggest that endosomal or lysosomal compartments regulate these pathways.
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