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      Principles of interleukin (IL)-6-type cytokine signalling and its regulation

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          Abstract

          The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.

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          Author and article information

          Journal
          Biochemical Journal
          Portland Press Ltd.
          0264-6021
          1470-8728
          August 15 2003
          August 15 2003
          : 374
          : 1
          : 1-20
          Affiliations
          [1 ]Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
          Article
          10.1042/bj20030407
          1223585
          12773095
          6012a483-0d73-4ecd-a577-5c5f6d797d15
          © 2003
          History

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