SIGNAL-TRANSDUCTION THROUGH GP130 THAT IS SHARED AMONG THE RECEPTORS FOR THE INTERLEUKIN-6 RELATED CYTOKINE SUBFAMILY

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.