Interleukin-6 family signal transducer (gp130) (gp130)

The Interleukin-6 family signal transducer, widely known as gp130 or CD130, is a foundational transmembrane protein that serves as the common signaling subunit for the entire IL-6 family of cytokines, including IL-6, IL-11, and leukemia inhibitory factor (UniProt P40189). It is expressed ubiquitously across various cell types, where it mediates critical physiological processes such as the acute-phase response, hematopoiesis, and bone metabolism (PubMed: 22476347). Upon the binding of a cytokine to its specific alpha-receptor, gp130 forms a functional signaling complex, typically through homodimerization or heterodimerization, which triggers the activation of the Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway (PubMed: 10455128). Dysregulation or overactivation of gp130-mediated signaling is a hallmark of numerous pathological conditions, particularly chronic inflammatory diseases like rheumatoid arthritis and various malignancies such as multiple myeloma and colorectal cancer (PubMed: 28438114). In oncology, constitutive activation of the gp130/STAT3 axis promotes tumor cell survival, proliferation, and angiogenesis, making it a high-priority therapeutic target. While many current clinical therapies, such as tocilizumab and siltuximab, target the IL-6 ligand or its alpha-receptor, newer strategies like olamkicept specifically target the gp130-mediated trans-signaling pathway to minimize systemic side effects (ClinicalTrials.gov: NCT03235752). Direct inhibition of gp130 using small molecules or monoclonal antibodies represents a potent approach to blocking the pleiotropic effects of multiple cytokines simultaneously. However, therapeutic intervention must be carefully managed due to the risk of serious infections and gastrointestinal complications associated with broad pathway suppression.

Other names

CD130IL6STInterleukin-6 receptor subunit betaGlycoprotein 130Oncostatin M receptor subunit alpha

Inhibition of gp130 dimerization and subsequent blockade of the JAK/STAT3, MAPK, and PI3K signaling pathways.