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PMID: 9311998 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL.

The EMBO journal ·Vol. 16 ·No. 17 ·1997-09-01 ·Pages 5386-97

Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT

Abstract

TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines and induces apoptosis in a wide variety of cells. Based on homology searching of a private database, a receptor for TRAIL (DR4 or TRAIL-R1) was recently identified. Here we report the identification of a distinct receptor for TRAIL, TRAIL-R2, by ligand-based affinity purification and subsequent molecular cloning. TRAIL-R2 was purified independently as the only receptor for TRAIL detectable on the surface of two different human cell lines that undergo apoptosis upon stimulation with TRAIL. TRAIL-R2 contains two extracellular cysteine-rich repeats, typical for TNF receptor (TNFR) family members, and a cytoplasmic death domain. TRAIL binds to recombinant cell-surface-expressed TRAIL-R2, and TRAIL-induced apoptosis is inhibited by a TRAIL-R2-Fc fusion protein. TRAIL-R2 mRNA is widely expressed and the gene encoding TRAIL-R2 is located on human chromosome 8p22-21. Like TRAIL-R1, TRAIL-R2 engages a caspase-dependent apoptotic pathway but, in contrast to TRAIL-R1, TRAIL-R2 mediates apoptosis via the intracellular adaptor molecule FADD/MORT1. The existence of two distinct receptors for the same ligand suggests an unexpected complexity to TRAIL biology, reminiscent of dual receptors for TNF, the canonical member of this family.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Apoptosis Apoptosis Regulatory Proteins B-Lymphocytes/metabolism Base Sequence Carrier Proteins/metabolism Chromosome Mapping Chromosomes, Human, Pair 8 Cloning, Molecular Cysteine Endopeptidases/metabolism Fas-Associated Death Domain Protein Humans Membrane Glycoproteins/metabolism Molecular Sequence Data RNA, Messenger/analysis Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor/genetics,isolation & purification,metabolism Sequence Analysis Sequence Homology, Amino Acid Serine Proteinase Inhibitors/pharmacology Signal Transduction TNF-Related Apoptosis-Inducing Ligand Tissue Distribution Tumor Necrosis Factor-alpha/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Apoptosis Regulatory Proteins Carrier Proteins FADD protein, human Fas-Associated Death Domain Protein Membrane Glycoproteins RNA, Messenger Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor Serine Proteinase Inhibitors TNF-Related Apoptosis-Inducing Ligand TNFRSF10B protein, human TNFSF10 protein, human Tumor Necrosis Factor-alpha Cysteine Endopeptidases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Walczak H
Immunex Corporation, 51 University Street, Seattle, WA 98101, USA.
Degli-Esposti M A
Johnson R S
Smolak P J
Waugh J Y
Boiani N
Timour M S
Gerhart M J
Schooley K A
Smith C A
Goodwin R G
Rauch C T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.17.5386
Published
1997-09-01
Pages
5386-97
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170170
Subset
IM
Databases
GENBANK
AF016849
External Links
PubMed source DOI: 10.1093/emboj/16.17.5386 PMC Full Text View journal details
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