Tumor necrosis factor (TNF) is a pleiotropic cytokine whose function is mediated
by two distinct cell surface receptors, designated TNF-R1 and TNF-R2,
which are expressed on most cell types. TNF function is primarily mediated
through TNF-R1 signaling. Both receptors belong to the growing TNF receptor
superfamily which includes FAS antigen and CD40. TNF-R1 contains a
cytoplasmic motif, termed the “death domain,” that has been found to be
necessary for the transduction of the apoptotic signal. The death domain is
also found in several other receptors, including FAS, DR2 (or TRUNDD), DR3
(Death receptor 3), DR4, DR5 and DR6. TRUNDD, DR4 and DR5 are receptors
for the apoptosis-inducing cytokine TRAIL. Non-death domain-containing
receptors, designated decoy receptor 1 (DcR1) or TRID, DcR2 and DcR3,
associate with specific ligands and may play a role in cellular resistance
to apoptotic stimuli.