Signal transduction through gp130 that is shared among the receptors for the interleukin 6 related cytokine subfamily

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Abstract
Interleukin 6 (IL‐6) and related cytokines, such as leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and IL‐11 exhibit multiple functions and redundancy in biological activities and play important roles in the immune response, hematopoiesis, the nervous system and acute phase reactions. These IL‐6 family cytokines exhibit a similar helical structure, and their receptors are structurally similar and constitute a cytokine receptor super family. In addition, a receptor subunit is shared among these IL‐6 related cytokine subfamily receptors, contributing to one of the mechanisms of functional redundancy of cytokine activities and suggesting the presence of a common signal transduction pathway among these receptors. In this review, we describe the structure of the receptors for IL‐6 and its related cytokine subfamily members. Furthermore, we propose a novel mechanism for the generation of cytokine diversity, i.e. the complex of a cytokine and one of its receptor subunits act as a novel cytokine on the cells that express the other receptor subunit(s) capable of acting as a receptor for the complex. Finally, we describe a Ras‐independent novel signal transduction pathway that utilizes Jak tyrosine kinase family, Stat protein family and yet unidentified H‐7‐sensitive pathway. This signal transduction pathway is commonly generated through the receptors for a wide range of cytokines and growth factors.

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