IL6 Signaling

IL(Interleukin)-6 is a pleiotropic cytokine playing a role in many physiological and pathological processes, including inflammation, hematopoiesis, and oncogenesis It participates in the regulation of cell growth, gene activation, proliferation, survival, and differentiation. IL-6 belongs to a family of related cytokines that includes leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin-1 (CTF1), ciliary neurotrophic factor (CNTF) etc. all of which initiate signaling through a signal transducing receptor (gp130, LIFR, OSMR). IL-6, IL-11 and CNTF first bind specifically to their respective non-signaling α-receptor subunits that are involved in recognition of the IL-6-type cytokines (IL-6Rα, IL11Rα, and CNTFRα). IL-6 stimulates homodimerization of gp130/IL6ST resulting in the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription). Other cytokines of the family (e.g., LIF, CTF1, CNTF, OSM) stimulate heterodimerization of LIFR and gp130. The signal transducing chains gp130, LIFR and OSMR binds to JAK1, JAK2 and TYK2 . Among these, JAK1 plays an essential role in IL6 signalling. All IL-6-type cytokines potently activate STAT3, and STAT1. SOCS proteins are the feedback inhibitors. SOCS1 and SOCS3 are functionally related and inhibit IL-6-type cytokine signalling. Gp130 is ubiquitously expressed and the specific cell response to a given IL-6 type cytokine, is the result of the restricted expression of the other receptor subunits (the alfa -receptor).