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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
1995-6-12
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pubmed:abstractText |
Interleukin-6 (IL-6) triggers the formation of a high affinity receptor complex constituted by the ligand-binding subunit IL-6 receptor alpha (IL-6R alpha) and the signal-transducing beta chain gp130. Since the cytoplasmic region of IL-6R alpha is not required for signal transduction, soluble forms of IL-6R alpha (sIL-6R alpha) show agonistic properties because they are still able to originate IL-6.sIL-6R alpha complexes, which in turn associate with gp130. A three-dimensional model of the human IL-6.IL-6R alpha.gp130 complex has been constructed and verified by site-directed mutagenesis of regions in shIL-6R alpha (where "h" is human) anticipated to contact hgp130, with the final goal of generating receptor variants with antagonistic properties. In good agreement with our structural model, substitutions at Asn-230, His-280, and Asp-281 selectively impaired the capability of shIL-6R alpha to associate with hgp130 both in vitro and on the cell surface, without affecting its affinity for hIL-6. Moreover, the multiple substitution mutant A228D/N230D/H280S/D281V expressed as a soluble protein partially antagonized hIL-6 bioactivity on hepatoma cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12242-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7744875-Amino Acid Sequence,
pubmed-meshheading:7744875-Animals,
pubmed-meshheading:7744875-Binding Sites,
pubmed-meshheading:7744875-Carcinoma, Hepatocellular,
pubmed-meshheading:7744875-Cell Line, Transformed,
pubmed-meshheading:7744875-Cercopithecus aethiops,
pubmed-meshheading:7744875-Computer Simulation,
pubmed-meshheading:7744875-Humans,
pubmed-meshheading:7744875-Interleukin-6,
pubmed-meshheading:7744875-Liver Neoplasms,
pubmed-meshheading:7744875-Macromolecular Substances,
pubmed-meshheading:7744875-Melanoma,
pubmed-meshheading:7744875-Models, Molecular,
pubmed-meshheading:7744875-Molecular Sequence Data,
pubmed-meshheading:7744875-Mutagenesis, Site-Directed,
pubmed-meshheading:7744875-Nucleopolyhedrovirus,
pubmed-meshheading:7744875-Protein Conformation,
pubmed-meshheading:7744875-Receptors, Interleukin,
pubmed-meshheading:7744875-Receptors, Interleukin-6,
pubmed-meshheading:7744875-Recombinant Fusion Proteins,
pubmed-meshheading:7744875-Sequence Alignment,
pubmed-meshheading:7744875-Sequence Homology, Amino Acid,
pubmed-meshheading:7744875-Signal Transduction,
pubmed-meshheading:7744875-Solubility,
pubmed-meshheading:7744875-Spodoptera,
pubmed-meshheading:7744875-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Interleukin-6 (IL-6) antagonism by soluble IL-6 receptor alpha mutated in the predicted gp130-binding interface.
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pubmed:affiliation |
Department of Genetics, Istituto di Ricerche di Biologia Molecolare P. Angeletti, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Comparative Study
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