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.
Hirano
T
T
Biomedical Research Center, Osaka University Medical School, Japan.
Matsuda
T
T
Nakajima
K
K
D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D001665:Binding Sites; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009857:Oncogenes; D018121:Receptors, Cytokine / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D016207:Cytokines; C494199:IL6ST protein, human; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130