Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
33
|
| pubmed:dateCreated |
1996-10-3
|
| pubmed:abstractText |
The high affinity interleukin-6 (IL-6) signaling complex consists of IL-6 and two membrane-associated receptor components: a low affinity but specific IL-6 receptor and the affinity converter/signal transducing protein gp130. Monomeric (IL-6M) and dimeric (IL-6D) forms of Escherichia coli-derived human IL-6 and the extracellular ("soluble") portions of the IL-6 receptor (sIL-6R) and gp130 have been purified in order to investigate the effect of IL-6 dimerization on binding to the receptor complex. Although IL-6D has a higher binding affinity for immobilized sIL-6R, as determined by biosensor analysis employing surface plasmon resonance detection, IL-6M is more potent than IL-6D in a STAT3 phosphorylation assay. The difference in potency is significantly less pronounced when measured in the murine 7TD1 hybridoma growth factor assay and the human hepatoma HepG2 bioassay due to time-dependent dissociation at 37 degrees C of IL-6 dimers into active monomers. The increased binding affinity of IL-6D appears to be due to its ability to cross-link two sIL-6R molecules on the biosensor surface. Studies of the IL-6 ternary complex formation demonstrated that the reduced biological potency of IL-6D resulted from a decreased ability of the IL-6D (sIL-6R)2 complex to couple with the soluble portion of gp130. These data imply that IL-6-induced dimerization of sIL-6R is not the driving force in promoting formation of the hexameric (IL-6 IL-6R gp130)2 complex. A model is presented whereby the trimeric complex of IL-6R, gp130, and IL-6M forms before the functional hexamer. Due to its increased affinity for the IL-6R but its decreased ability to couple with gp130, we suggest that a stable IL-6 dimer may be an efficient IL-6 antagonist.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokine Receptor gp130,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IL6ST protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
16
|
| pubmed:volume |
271
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
20138-44
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8702737-Antigens, CD,
pubmed-meshheading:8702737-Cytokine Receptor gp130,
pubmed-meshheading:8702737-DNA-Binding Proteins,
pubmed-meshheading:8702737-Humans,
pubmed-meshheading:8702737-Interleukin-6,
pubmed-meshheading:8702737-Kinetics,
pubmed-meshheading:8702737-Macromolecular Substances,
pubmed-meshheading:8702737-Membrane Glycoproteins,
pubmed-meshheading:8702737-Molecular Weight,
pubmed-meshheading:8702737-Phosphotyrosine,
pubmed-meshheading:8702737-Protein Binding,
pubmed-meshheading:8702737-Receptor Aggregation,
pubmed-meshheading:8702737-Receptors, Interleukin,
pubmed-meshheading:8702737-Receptors, Interleukin-6,
pubmed-meshheading:8702737-Recombinant Proteins,
pubmed-meshheading:8702737-STAT3 Transcription Factor,
pubmed-meshheading:8702737-Signal Transduction,
pubmed-meshheading:8702737-Trans-Activators
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Influence of interleukin-6 (IL-6) dimerization on formation of the high affinity hexameric IL-6.receptor complex.
|
| pubmed:affiliation |
Joint Protein Structure Laboratory, Ludwig Institute for Cancer Research (Melbourne), Vicotoria, Australia.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|