The JAK–STAT pathway is a direct route from cytokine receptors to gene transcription. For the IL-6 cytokine family, which signals through the shared receptor subunit gp130, it is central to immunity, inflammation and the acute-phase response.
How JAK–STAT works
- A cytokine (e.g. IL-6) binds its receptor, which dimerises and recruits gp130.
- Receptor-associated JAK kinases (JAK1, JAK2, TYK2) trans-phosphorylate each other and the receptor.
- STAT proteins (mainly STAT3 for IL-6) dock, are phosphorylated, dimerise and translocate to the nucleus to drive transcription.
The IL-6 family and gp130
IL-6, IL-11, LIF, OSM, CNTF and related cytokines all use gp130 as a shared signal-transducing subunit, which is why they have overlapping effects. IL-6 also signals via trans-signalling (soluble IL-6 receptor), broadening the range of responsive cells — relevant to chronic inflammation.
Why it matters
The pathway is regulated by SOCS proteins (negative feedback) and is a major drug target: IL-6/IL-6R blockers (e.g. tocilizumab) and JAK inhibitors are used in rheumatoid arthritis and other inflammatory diseases.
Explore the pathway
- KEGG: JAK–STAT signalling pathway
- Reactome — search “Interleukin-6 signaling”.
- Cell Signaling Technology pathways
Frequently asked questions
What does the JAK-STAT pathway do?
It transmits cytokine signals directly to the nucleus: JAK kinases phosphorylate STAT transcription factors, which then drive gene expression.
What is gp130?
The shared signal-transducing receptor subunit used by the IL-6 family of cytokines.
How is the pathway targeted therapeutically?
With IL-6/IL-6R inhibitors (e.g. tocilizumab) and JAK inhibitors, used in inflammatory and autoimmune diseases.
