The N-terminal cytokine binding domain of LIFR is required for CNTF binding and signaling.
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.
He
Wei
W
Department of Biochemistry and Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Gong
Ke
K
Smith
David K
DK
Ip
Nancy Y
NY
D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D017384:Sequence Deletion; D015398:Signal Transduction / Q000187:drug effects
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C508351:OSM protein, human; D010455:Peptides; D011506:Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053683:Oncostatin M