Leukemia inhibitory factor receptor and glycoprotein 130 (LIFR and gp130)

The leukemia inhibitory factor receptor and glycoprotein 130 (LIFR and gp130) form a heterodimeric receptor complex essential for transducing signals from leukemia inhibitory factor (LIF) and other cytokines of the interleukin-6 (IL-6) family. LIF binds with high affinity to both LIFR and gp130, triggering receptor dimerization and activation of intracellular signaling, predominantly via the JAK/STAT3 pathway, but also involving MAPK/ERK and PI3K/AKT pathways[3][6]. Gp130 is a shared subunit for multiple cytokine receptors, acting as the common signal-transducing element for the IL-6 family[1][5]. These receptors are structurally characterized by extracellular immunoglobulin-like and fibronectin-III domains[1][5]. They play diverse roles in stem cell maintenance, immune regulation, cardiac function, neural development, inflammation, and tumorigenesis[6][2][5]. Disrupting LIFR/gp130 function has been associated with various pathologies, ranging from cancer and chronic inflammation to cardiac and neurological disorders. LIFR and gp130 are validated targets for modulating cytokine signaling in applicable disease settings, but their broad physiological roles present therapeutic challenges related to specificity and safety[6][2][5].

Other names

LIF receptor (LIFR)Glycoprotein 130 (gp130)IL6ST (for gp130)CD130 (for gp130)IL-6 receptor beta (for gp130)LIFRβ (for LIFR)

Ligand blockade (e.g., antibodies or antagonists prevent LIF or IL-6 from binding LIFR/gp130 complex). Downregulation of signaling (inhibition of receptor dimerization or JAK/STAT pathway downstream). Modulation of JAK/STAT, MAPK/ERK, and PI3K/AKT signaling cascades mediated by receptor activation.