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PMID: 9603945 Published · ppublish English Journal Article

Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.

The Journal of biological chemistry ·Vol. 273 ·No. 23 ·1998-06-05 ·Pages 14363-7

Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR

Abstract

TRAIL is a tumor necrosis factor-related ligand that induces apoptosis upon binding to its death domain-containing receptors, DR4 and DR5. Two additional TRAIL receptors, TRID/DcR1 and DcR2, lack functional death domains and function as decoy receptors for TRAIL. We have identified a fifth TRAIL receptor, namely osteoprotegerin (OPG), a secreted tumor necrosis factor receptor homologue that inhibits osteoclastogenesis and increases bone density in vivo. OPG-Fc binds TRAIL with an affinity of 3.0 nM, which is slightly weaker than the interaction of TRID-Fc or DR5-Fc with TRAIL. OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL.

MeSH Terms
Animals Apoptosis/physiology Apoptosis Regulatory Proteins Binding, Competitive GPI-Linked Proteins Glycoproteins/physiology Humans Immunoglobulin Fc Fragments/genetics Immunohistochemistry Jurkat Cells Ligands Membrane Glycoproteins/physiology Mice Microscopy, Fluorescence Oligopeptides Osteoclasts/cytology Osteoprotegerin Peptides/immunology Protein Binding/physiology Receptors, Cytoplasmic and Nuclear Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor/classification,metabolism,physiology Receptors, Tumor Necrosis Factor, Member 10c Receptors, Tumor Necrosis Factor, Member 25 Recombinant Fusion Proteins/metabolism TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor Decoy Receptors Tumor Necrosis Factor-alpha/physiology
Chemicals
Apoptosis Regulatory Proteins GPI-Linked Proteins Glycoproteins Immunoglobulin Fc Fragments Ligands Membrane Glycoproteins Oligopeptides Osteoprotegerin Peptides Receptors, Cytoplasmic and Nuclear Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Member 10c Receptors, Tumor Necrosis Factor, Member 25 Recombinant Fusion Proteins TNF-Related Apoptosis-Inducing Ligand TNFRSF10B protein, human TNFRSF10C protein, human TNFRSF11B protein, human TNFRSF25 protein, human TNFSF10 protein, human Tnfrsf10b protein, mouse Tnfrsf11b protein, mouse Tnfrsf25 protein, mouse Tnfsf10 protein, mouse Tumor Necrosis Factor Decoy Receptors Tumor Necrosis Factor-alpha FLAG peptide
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Emery J G
Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA.
McDonnell P
Burke M B
Deen K C
Lyn S
Silverman C
Dul E
Appelbaum E R
Eichman C
DiPrinzio R
Dodds R A
James I E
Rosenberg M
Lee J C
Young P R
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
Published
1998-06-05
Pages
14363-7
Language
English
Region
United States
NLM ID
2985121R
Subset
IM
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