IL6ST

Functions as a shared signal-transducing subunit not only for IL6 but also for other cytokine receptor complexes, including IL6, LIF, OSM, CNTF, IL11, CTF1, BSF3, MT-RNR2/humanin, CLCF1 and the heterodimeric complex CRLF1-CLCF1. Engages site 2 of CNTF, CLCF1, LIF, and IL-6, and site 3 of IL27 and IL6. Initiates signal transmission through three mechanisms. Binding of cytokines, such as IL6 or IL11 to the alpha-chains of their specific cell surface receptor triggers homodimerization of IL6ST/gp130. In contrast, binding of other IL-6 family cytokines can result in the formation of a IL6ST/gp130 heterodimer with another signal-transducing receptor, such as LIFR or OSMR. Moreover, binding of CNTF or CLCF1 or the heterodimeric complex CRLF1-CLCF1 or MT-RNR2/humanin to the non-signaling receptor CNTFR induces heterodimerization of the IL6ST/gp130 with LIFR or IL27RA/WSX1 (in the case of MT-RNR2/humanin). Mechanistically, homodimerization or heterodimerization of IL6ST/gp130 activate JAK tyrosine kinases bound to their intracellular domains. These kinases subsequently phosphorylate the homodimer or heterodimer form of IL6ST/gp130. The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STATs). The IL6 signaling pathway induces, in parallel, the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity)..

Function from UniProtKB (P40189), read 2026-09-23. CC BY 4.0.