Tumor necrosis factor receptor and Fas signaling mechanisms

Four members of the tumor necrosis factor (TNF) ligand family, TNF-alpha, L T-alpha, LT-beta, and LIGHT, interact with four receptors of the TNF/nerve growth factor family, the p55 TNF receptor (CD120a), the p75 TNF receptor ( CD120b), the lymphotoxin beta receptor (LT beta R), and herpes virus entry mediator (HVEM) to control a wide range of innate and adaptive immune respo nse functions. Of these, the most thoroughly studied are cell death inducti on and regulation of the inflammatory process. Fas/Apo1 (CD95), a receptor of the TNF receptor family activated by a distinct ligand, induces death in cells through mechanisms shared with CD120a. The last four years have seen a proliferation in knowledge of the proteins participating in the signalin g by the TNF system and CD95. The downstream signaling molecules identified so far-caspases, phospholipases, the three known mitogen activated protein (MAP) kinase pathways, and the NF-kappa B activation cascade-mediate the e ffects of other inducers as well. However, the molecules that initiate thes e signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor re ceptor family.