Biochem J 2003 May 29;Pt
Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F.
The IL-6-type cytokines IL-6, IL-11, LIF, OSM, CNTF, CT-1 and CLC 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 hematopoiesis, liver and neuronal regeneration, embryonal development and fertility.
Dysregulation of IL-6-type cytokine signaling 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 gp130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT and MAPK 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 signaling pathway mediated by tyrosine phosphatases, the SOCS feedback inhibitors and PIAS proteins.
Also the cross-talk between the JAK/STAT pathway with other signaling cascades is dicussed.