Glycoprotein 130 receptor subunit (gp130)

Glycoprotein 130 is a type I transmembrane protein that acts as the common signal transducing subunit shared by a family of cytokine receptors, notably those for interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1)[3][5][7]. It is structurally characterized by an extracellular region composed of immunoglobulin-like and fibronectin type III domains, a single transmembrane domain, and a cytoplasmic tail essential for recruitment and activation of cytoplasmic kinases. Upon cytokine receptor engagement and gp130 dimerization (as a homodimer or heterodimer with other tall cytokine receptors), it mediates intracellular signaling primarily through the JAK/STAT pathway, as well as MAPK and PI3K pathways, to regulate inflammation, immune responses, cell proliferation, hematopoiesis, neuronal survival, and metabolic processes[1][2][4][5][6]. Gp130-mediated signaling is implicated in the pathogenesis of various diseases including cancer, autoimmune disorders, chronic inflammation, and metabolic syndrome, making it a validated and actively pursued therapeutic target[7]. Drugs such as olamkicept target gp130 to modulate these signaling cascades for clinical benefit, but systemic inhibition may lead to safety risks due to the wide physiological roles of this receptor subunit.

Other names

IL6STIL-6 signal transducerInterleukin-6 receptor subunit betaCD130IL6R-betamembrane glycoprotein 130

Inhibition of gp130-mediated cytokine signaling (JAK/STAT pathway blockade); Modulation of receptor complex assembly and downstream phosphorylation events; Inhibition of pro-inflammatory transcription factors via STAT3/STAT1 pathway modulation