A death-domain-containing receptor that mediates apoptosis.
The cell-killing effects of the cytokines TNF-alpha and FasL are mediated by the distinct cell-surface receptors TNFR1, TNFR2 and Fas (also known as CD95/APO-1), which are all members of a receptor superfamily that is important for regulating cell survival. The cytoplasmic regions of TNFR1 and Fas contain a conserved 'death' domain which is an essential component of the signal pathway that triggers apoptosis and activation of the transcription factor NF-kappaB (refs 5,6). Here we report the isolation of a 54K receptor that is a new member of the TNFR superfamily, using the death domain of TNFR1 in a yeast two-hybrid system. This protein, WSL-1, is most similar to TNFR1 itself, particularly in the death-domain region. The gene wsl-1 is capable of inducing apoptosis when transfected into 3T3 and 293 cells, and can also activate NF-kappaB in 293 cells. Like TNFR1, WSL-1 will homodimerize in yeast. WSL-1 also interacts specifically with the TNFR1-associated molecule TRADD. The tissue distribution is very restricted and significantly different from that of Fas and TNFR1.
Kitson
J
J
Cell Biology Unit, Glaxo-Wellcome Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, UK.
Raven
T
T
Jiang
Y P
YP
Goeddel
D V
DV
Giles
K M
KM
Pun
K T
KT
Grinham
C J
CJ
Brown
R
R
Farrow
S N
SN
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry; D017209:Apoptosis; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047888:Receptors, Tumor Necrosis Factor, Type I; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047888:Receptors, Tumor Necrosis Factor, Type I; C506033:TNFRSF25 protein, human