Tumor necrosis factor receptor and Fas signaling mechanisms

Annu Rev Immunol. 1999;17:331-67. doi: 10.1146/annurev.immunol.17.1.331.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Caspases / metabolism
  • Humans
  • Ligands
  • Lipids / immunology
  • Phospholipases / metabolism
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Kinases / metabolism
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism
  • fas Receptor / metabolism*


  • Ligands
  • Lipids
  • Receptors, Tumor Necrosis Factor
  • Transcription Factors
  • fas Receptor
  • Protein Kinases
  • Phospholipases
  • Phosphoric Monoester Hydrolases
  • Caspases