Leukemia inhibitory factor receptor–glycoprotein 130 complex (LIFR–gp130 complex)

The leukemia inhibitory factor receptor–glycoprotein 130 complex is a cell-surface heterodimeric receptor critical for the signaling of leukemia inhibitory factor (LIF), a polyfunctional cytokine of the IL-6 family[5][6][7]. The high-affinity receptor complex is composed of leukemia inhibitory factor receptor (LIFR, CD118) and glycoprotein 130 (gp130, IL6ST, CD130), both members of the type I cytokine receptor family[1][7][9]. Upon binding LIF, the receptor chains dimerize, activating intracellular Janus kinases (JAK), which in turn phosphorylate and activate STAT proteins (especially STAT3), as well as other pathways such as PI3K–AKT and MAPK[6][8]. This signaling regulates cell differentiation, survival, proliferation, and pluripotency, and is vital in embryonic development, immune regulation, and oncogenesis[4][5][6]. Aberrant signaling through this receptor complex is implicated in multiple disease states including cancer (both metastasis suppression and progression, depending on context), inflammation, and tissue regeneration[4][7]. Due to its wide biological impact, the LIFR–gp130 complex is an active focus for drug discovery with implications for targeted cancer therapies, but presents safety challenges due to pleiotropic signaling.

Other names

LIFR–gp130 heterodimerLIF receptor complexLeukemia inhibitory factor receptor–IL6ST complexCD118–CD130 complexLIFRβ–gp130 complexLIF receptor high-affinity complex

Ligand blockade (LIF/LIFR binding blockade); Inhibition of downstream signaling (JAK/STAT3, PI3K/AKT pathway inhibition); Disruption of receptor dimerization/complex formation; Selective allosteric modulation (investigational)