The N‐terminal cytokine binding domain of LIFR is required for CNTF binding and signaling

• DOI: 10.1016/j.febslet.2005.06.061
• Publication Date: 2005-07-19T14:20:40Z
• Authors: Wei He; Ke Gong; David K. Smith; Nancy Y. Ip
• Keywords: 0301 basic medicine; Ciliary neurotrophic factor; Leukemia Inhibitory Factor Receptor alpha Subunit; Receptors, OSM-LIF; Interleukin-6; Proteins; Oncostatin M; Leukemia Inhibitory Factor; Protein Structure, Tertiary; gp130; 03 medical and health sciences; Leukemia inhibitory factor; Gp130; Protein Interaction Mapping; Cytokines; Humans; Neuropoietic cytokine; Ciliary Neurotrophic Factor; Receptors, Cytokine; Peptides; Receptor, Ciliary Neurotrophic Factor; Protein Binding; Sequence Deletion; Signal Transduction

Ciliary neurotrophic factor (CNTF) forms a functional receptor complex containing the CNTF receptor, gp130, and the leukemia inhibitory factor receptor (LIFR). However, the nature and stoichiometry of the receptor‐mediated interactions in this complex have not yet been fully resolved. We show here that signaling by CNTF, but not by LIF or oncostatin M (OSM), was abolished in cells overexpressing a LIFR mutant with the N‐terminal cytokine binding domain deleted. Our results illustrate molecular differences between the CNTF active receptor complex and those of LIF and OSM and provide further support for the hexameric model of the CNTF receptor complex.