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Structure-function analysis of human IL-6 receptor: dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130.

1993; Springer Nature; Volume: 12; Issue: 4 Linguagem: Inglês

10.1002/j.1460-2075.1993.tb05815.x

1460-2075

Hideo Yawata, Kiyoshi Yasukawa, Shunji Natsuka, Masaaki Murakami, Katsuhiko Yamasaki, Masahiko Hibi, Tetsuya Taga, Tadamitsu Kishimoto,

Cytokine Signaling Pathways and Interactions

Research Article1 April 1993free access Structure-function analysis of human IL-6 receptor: dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130. H. Yawata H. Yawata Division of Immunology, Osaka University, Japan. Search for more papers by this author K. Yasukawa K. Yasukawa Division of Immunology, Osaka University, Japan. Search for more papers by this author S. Natsuka S. Natsuka Division of Immunology, Osaka University, Japan. Search for more papers by this author M. Murakami M. Murakami Division of Immunology, Osaka University, Japan. Search for more papers by this author K. Yamasaki K. Yamasaki Division of Immunology, Osaka University, Japan. Search for more papers by this author M. Hibi M. Hibi Division of Immunology, Osaka University, Japan. Search for more papers by this author T. Taga T. Taga Division of Immunology, Osaka University, Japan. Search for more papers by this author T. Kishimoto T. Kishimoto Division of Immunology, Osaka University, Japan. Search for more papers by this author H. Yawata H. Yawata Division of Immunology, Osaka University, Japan. Search for more papers by this author K. Yasukawa K. Yasukawa Division of Immunology, Osaka University, Japan. Search for more papers by this author S. Natsuka S. Natsuka Division of Immunology, Osaka University, Japan. Search for more papers by this author M. Murakami M. Murakami Division of Immunology, Osaka University, Japan. Search for more papers by this author K. Yamasaki K. Yamasaki Division of Immunology, Osaka University, Japan. Search for more papers by this author M. Hibi M. Hibi Division of Immunology, Osaka University, Japan. Search for more papers by this author T. Taga T. Taga Division of Immunology, Osaka University, Japan. Search for more papers by this author T. Kishimoto T. Kishimoto Division of Immunology, Osaka University, Japan. Search for more papers by this author Author Information H. Yawata1, K. Yasukawa1, S. Natsuka1, M. Murakami1, K. Yamasaki1, M. Hibi1, T. Taga1 and T. Kishimoto1 1Division of Immunology, Osaka University, Japan. The EMBO Journal (1993)12:1705-1712https://doi.org/10.1002/j.1460-2075.1993.tb05815.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Here, we report the analysis of the structure-function relationship of the extracellular region of human interleukin 6 receptor (IL-6R). Upon binding of IL-6, IL-6R becomes associated extracellularly with a non-IL-6-binding but signal transducing molecule, gp130, and the IL-6 signal is generated. In this region, the cytokine receptor family domain, but not the immunoglobulin-like domain, was responsible both for IL-6 binding and for signal transduction through gp130. Because a soluble, extracellular portion of IL-6R (sIL-6R) could bind IL-6 and mediate IL-6 functions through gp130, amino acid substitutions were introduced into sIL-6R by site-directed mutagenesis. The results, together with the previously proposed tertiary structure model, suggested that the amino acid residues critical for IL-6 binding have a tendency to be distributed to the hinge region between the two 'barrel'-like fibronectin type III modules and to the same side of these two 'barrels'. Amino acid residues, of which substitutions barely affected the IL-6-binding but did abolish the IL-6 signalling capability of sIL-6R, were identified and found to be located mainly in the membrane proximal half of the second barrel. sIL-6R mutants carrying such substitutions lacked the capacity to associate with gp130 in the presence of IL-6. Previous ArticleNext Article Volume 12Issue 41 April 1993In this issue RelatedDetailsLoading ...