CNTFR

Functions either as a membrane-anchored non-signaling receptor via a GPI anchor or, after proteolytic release, as a soluble ligand-binding chaperone, and mediates signaling of CNTF-related cytokines, including ciliary neurotrophic factor (CNTF), cardiotrophin-like cytokine factor 1 (CLCF1), and the heterodimeric cytokine formed by CLCF1 and the cytokine receptor-like factor 1 (CRLF1). Involved namely in cell survival of motor neurons and regulation of oligodendrocyte progenitor proliferation. Functions within the ciliary neurotrophic factor receptor (CNTFR) complex as a membrane-anchored non-signaling receptor subunit associated with two other signaling receptor subunits IL6ST/gp130 and LIFR. Also, functions within the humanin receptor complex as a membrane-anchored non-signaling receptor subunit associated with IL6ST/GP130 and IL27RA/WSX1 that mediates the MT-RNR2/humanin signaling which induces neuroprotection. Alternatively functions as a soluble ligand-binding chaperone that binds ligand in the extracellular space, forming a cytokine complex which is delivered to the IL6ST/gp130 and LIFR signaling receptor subunits. Mechanistically, ligand binding to the CNTFR induces dimerization of the IL6ST/gp130 and LIFR (or IL27RA/WSX1 in the case of MT-RNR2/humanin), which activate JAK tyrosine kinases (JAK1 or JAK2 and to lesser extent TYK2) bound to their intracellular domains. These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (or IL27RA/WSX1). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STAT3 and to lesser extent STAT1)..

Function from UniProtKB (P26992), read 2026-09-23. CC BY 4.0.