IL-6 Receptor

Hibi M., Hirano T.

Interleukin 6 (IL-6) is a pleiotropic cytokine that regulates immune reaction, hematopoiesis, and differentiation of the nervous system. The receptor for IL-6 (IL-6R) consists of two chains, namely IL-6R♂ and gp130. Both IL-6R♂ and gp130 belong to thetype I cytokine receptor superfamily. IL-6R♂ is the binding component specific to IL-6. In contrast, gp130 transmits signals not only of IL-6 but also of IL-6-related cytokines such as leukemia-inhibitory factor (LIF), ciliary neurotropic factor (CNTF), oncostatin M (OSM), IL-11, cardiotropin 1 (CT-1), and possibly neurotrophin-1/B cell-stimulating factor3 (NNT-1/BSF-3). The ligand’s binding to the receptor leads to homo- and eterodimerization of gp130, resulting in the activation of gp130-associated JAKs (JAK1, JAK2, and TYK2) and subsequently tyrosine phosphorylation of gp130. The tyrosine phosphorylated gp130 further transmits signals by recruiting SH2 domain-containing signaling molecules such as the protein tyrosine phosphatase SHP-2 and STAT1 and STAT3 (signal transducers and activators of transcription). We describe the roles of these signal transduction pathways in the biological responses of the IL-6 family cytokines.