Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL

J Biol Chem. 1997 Oct 10;272(41):25417-20. doi: 10.1074/jbc.272.41.25417.

Abstract

A human receptor for the cytotoxic ligand TRAIL (TRAIL receptor-1, designated DR4) was identified recently as a member of the tumor necrosis factor receptor family. In this report we describe the identification of two additional human TRAIL receptors, TRAIL receptor-2 and TRAIL receptor-3, that belong to the tumor necrosis factor receptor family. Interestingly, TRAIL receptor-2 but not TRAIL receptor-3 contains a cytoplasmic "death domain" necessary for induction of apoptosis and is hence designated death receptor-5 (DR5). Like DR4, DR5 engages the apoptotic pathway independent of the adaptor molecule FADD/MORT1. Because of its lack of a death domain, TRAIL receptor-3 is not capable of inducing apoptosis. However, by competing for TRAIL, it is capable of inhibiting TRAIL-induced apoptosis. Thus, TRAIL receptor-3 may function as an antagonistic decoy receptor to attenuate the cytotoxic effect of TRAIL in most tissues that are TRAIL+, DR4+, and DR5+.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Arabidopsis Proteins*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / metabolism
  • Caspase 1
  • Caspase 10
  • Caspases*
  • Cloning, Molecular
  • Cysteine Endopeptidases / metabolism
  • Fas-Associated Death Domain Protein
  • Fatty Acid Desaturases / metabolism
  • GPI-Linked Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Molecular Sequence Data
  • Plant Proteins / metabolism
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / genetics*
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Tumor Necrosis Factor Decoy Receptors

Substances

  • Adaptor Proteins, Signal Transducing
  • Arabidopsis Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • GPI-Linked Proteins
  • Intracellular Signaling Peptides and Proteins
  • Plant Proteins
  • Receptors, Cell Surface
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 10c
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFRSF10C protein, human
  • Tumor Necrosis Factor Decoy Receptors
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • Caspase 10
  • Caspases
  • Cysteine Endopeptidases
  • interleukin 1beta-converting enzyme 2
  • Caspase 1

Associated data

  • GENBANK/AF020501
  • GENBANK/AF020502