Interleukin 6 signal transducer (gp130)–Signal transducer and activator of transcription 3 (STAT3) signaling pathway (gp130–STAT3 pathway)

The gp130–STAT3 signaling pathway is a fundamental signal transduction axis that mediates the pleiotropic effects of the interleukin-6 (IL-6) family of cytokines. The process begins when cytokines like IL-6 bind to their specific receptors, triggering the recruitment and dimerization of the common transmembrane glycoprotein gp130 (also known as IL6ST or CD130) [UniProt: P40189]. This dimerization activates associated Janus kinases (JAKs), which phosphorylate tyrosine residues on the cytoplasmic tail of gp130, providing docking sites for the Signal Transducer and Activator of Transcription 3 (STAT3) [PubMed: 26343580]. Once recruited, STAT3 is phosphorylated, forms homodimers, and translocates to the nucleus where it acts as a transcription factor for genes promoting cell proliferation, survival, and pro-inflammatory responses [UniProt: P40763]. In many human cancers, this pathway is constitutively active, driving tumor progression, metastasis, and immune evasion, while in autoimmune diseases, it fuels chronic inflammation [PubMed: 30610225]. Therapeutic strategies targeting this pathway include monoclonal antibodies against IL-6 or its receptor (e.g., Tocilizumab), small molecule JAK inhibitors (e.g., Ruxolitinib), and emerging direct STAT3 inhibitors or gp130 antagonists [PubMed: 29346074].

Other names

gp130-STAT3 axisIL-6/gp130/STAT3 pathwayCD130-STAT3 signalingIL6ST-STAT3 pathway

Inhibition of cytokine binding to gp130-containing receptors, inhibition of JAK kinase activity, or direct inhibition of STAT3 phosphorylation, dimerization, and DNA binding.