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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Review Article|
August 15 2003
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
Peter C. HEINRICH;
Peter C. HEINRICH
2
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
2To whom correspondence should be addressed (e-mail [email protected]).
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Iris BEHRMANN;
Iris BEHRMANN
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
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Serge HAAN;
Serge HAAN
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
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Heike M. HERMANNS;
Heike M. HERMANNS
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
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Gerhard MÜLLER-NEWEN;
Gerhard MÜLLER-NEWEN
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
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Fred SCHAPER
Fred SCHAPER
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
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Publisher: Portland Press Ltd
Received:
March 13 2003
Revision Received:
April 30 2003
Accepted:
May 29 2003
Accepted Manuscript online:
May 29 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 374 (1): 1–20.
Article history
Received:
March 13 2003
Revision Received:
April 30 2003
Accepted:
May 29 2003
Accepted Manuscript online:
May 29 2003
Citation
Peter C. HEINRICH, Iris BEHRMANN, Serge HAAN, Heike M. HERMANNS, Gerhard MÜLLER-NEWEN, Fred SCHAPER; Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 15 August 2003; 374 (1): 1–20. doi: https://doi.org/10.1042/bj20030407
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