Tumor necrosis factor receptor and Fas signaling mechanisms.
Four members of the tumor necrosis factor (TNF) ligand family, TNF-alpha, LT-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 response functions. Of these, the most thoroughly studied are cell death induction 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 signaling 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 effects of other inducers as well. However, the molecules that initiate these 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 receptor family.
Wallach
D
D
Department of Biological Chemistry, Weizmann Institute, Rehovot, Israel. lvwalach@weizmann.weizmann.ac.il
Varfolomeev
E E
EE
Malinin
N L
NL
Goltsev
Y V
YV
Kovalenko
A V
AV
Boldin
M P
MP
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000276:immunology; D010740:Phospholipases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D008024:Ligands; D008055:Lipids; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D019014:fas Receptor; D011494:Protein Kinases; D010740:Phospholipases; D010744:Phosphoric Monoester Hydrolases; D020169:Caspases