Source:http://linkedlifedata.com/resource/pubmed/id/17548657
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2007-6-5
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| pubmed:abstractText |
TWEAK (TNF-like weak inducer of apoptosis) is a TNF superfamily member implicated in several mechanisms. Although fibroblast growth factor inducible 14 (Fn14)/TweakR has been reported as its receptor, an as yet unrecognized surface molecule(s) might modulate TWEAK function(s). Thus, we set out to identify TWEAK-binding proteins by screening a combinatorial peptide library. Cyclic peptides containing a consensus motif (WXDDG) bound to TWEAK specifically. These peptides were similar to CD163, a scavenger receptor cysteine-rich domain family member, restricted to the monocyte/macrophage lineage and responsible for the uptake of circulating haptoglobin-hemoglobin (Hp-Hb) complexes. Sequence profile analysis suggested that TWEAK mimicked the CD163 natural ligand (Hp-Hb). Consistently, we show dose-dependent TWEAK binding to CD163 and blockade by an anti-CD163 Ab. In a competition assay, both soluble CD163 and Fn14/TweakR were able to compete off TWEAK binding to coated Fn14/TweakR or CD163, respectively. Flow-cytometry and immunofluorescence assays showed that human monocytes (Fn14/TweakR negative and CD163 positive) bind TWEAK, thus blocking the recognition of CD163 and reducing the activation mediated by a specific mAb in these cells. We demonstrate that monocytes can sequester TWEAK from supernatants, thus preventing tumor cell apoptosis; this effect was reverted by preincubation with the peptide mimicking CD163 or with a mAb anti-CD163, indicating specificity. Finally, we show that recombinant human TWEAK binding to CD163-transfected Chinese hamster ovary cells is inhibited by the presence of either unlabeled TWEAK or the Hp-Hb complex. Together, these data are consistent with the hypothesis that CD163 either acts as a TWEAK scavenger in pathological conditions or serves as an alternate receptor for TWEAK in cells lacking Fn14/TweakR.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD163 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TWEAK receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
178
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
8183-94
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| pubmed:dateRevised |
2007-12-3
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| pubmed:meshHeading |
pubmed-meshheading:17548657-Amino Acid Sequence,
pubmed-meshheading:17548657-Animals,
pubmed-meshheading:17548657-Antibodies, Monoclonal,
pubmed-meshheading:17548657-Antigens, CD,
pubmed-meshheading:17548657-Antigens, Differentiation, Myelomonocytic,
pubmed-meshheading:17548657-CHO Cells,
pubmed-meshheading:17548657-Cricetinae,
pubmed-meshheading:17548657-Cricetulus,
pubmed-meshheading:17548657-Humans,
pubmed-meshheading:17548657-Iodine Radioisotopes,
pubmed-meshheading:17548657-Ligands,
pubmed-meshheading:17548657-Molecular Sequence Data,
pubmed-meshheading:17548657-Monocytes,
pubmed-meshheading:17548657-Peptide Library,
pubmed-meshheading:17548657-Peptides,
pubmed-meshheading:17548657-Protein Interaction Mapping,
pubmed-meshheading:17548657-Receptors, Cell Surface,
pubmed-meshheading:17548657-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:17548657-Recombinant Proteins,
pubmed-meshheading:17548657-Tumor Necrosis Factors
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| pubmed:year |
2007
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| pubmed:articleTitle |
A previously unrecognized protein-protein interaction between TWEAK and CD163: potential biological implications.
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| pubmed:affiliation |
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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