IL-6 receptor and mechanism of signal transduction.
Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety of cells, exerting growth promotion, growth inhibition, or specific gene expression including cellular differentiation. The IL-6 receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R) and a non-ligand-binding signal transducer, gp130, both of which belong to the cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL-6R and gp130, and gp130 in turn transduces the signal. Despite its lack of IL-6 binding property, gp130 is involved in the formation of high-affinity IL-6 binding sites. This two-chain IL-6 receptor system can be applied to some other cytokine receptors, such as IL-3R, IL-5R and GM-CSFR which share a second signal-transducing component. A nuclear factor for controlling IL-6 gene expression (NF-IL6) is a leucine zipper-containing transcription factor and is homologous to C/EBP, a liver nuclear factor. NF-IL6 is also involved in the transcriptional regulation of various acute phase protein genes IL-6-triggered association of IL-6R and gp130 on hepatocytes, through intermediate steps including serine-phosphorylation of pre-existing NF-IL6 protein, leads to binding of NF-IL6 to IL-6-responsive elements and activation of acute-phase protein genes.
Kishimoto
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Division of Immunology, Osaka University, Japan.
Akira
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Taga
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D014157:Transcription Factors