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PMID: 12773095 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

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

The Biochemical journal ·Vol. 374 ·No. Pt 1 ·2003-08-15 ·Pages 1-20

Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F

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.

MeSH Terms
Animals Cytokines/chemistry,physiology Humans Infections/immunology Interleukin-6/chemistry,physiology Models, Molecular Phosphorylation Protein Conformation Protein Structure, Secondary Receptors, Interleukin-6/physiology Signal Transduction/immunology Wounds and Injuries/immunology
Chemicals
Cytokines Interleukin-6 Receptors, Interleukin-6
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Heinrich Peter C
Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany. heinrich@rwth-aachen.de
Behrmann Iris
Haan Serge
Hermanns Heike M
Müller-Newen Gerhard
Schaper Fred
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/BJ20030407
Email
heinrich@rwth-aachen.de
Published
2003-08-15
Pages
1-20
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1223585
Subset
IM
External Links
PubMed source DOI: 10.1042/BJ20030407 PMC Full Text View journal details
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