title: Binding interactions of leukemia inhibitory factor and ciliary neurotrophic factor with the different subunits of their high affinity receptors.
abstract: Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) share common components in their multimeric receptors. Both cytokine receptors contain gp130/interleukin-6-receptor transducer as well as gp190/low affinity LIF receptor. For CNTF, addition of a third subunit, or alpha subunit, defines the high-affinity CNTF receptor. In the present study, we analyzed the binding interactions of LIF and CNTF in human cell lines and showed a mutual displacement for LIF and CNTF toward the trimeric high-affinity CNTF receptor. Similar results were obtained in the JEG cell line, which only expressed the gp130/gp190 high-affinity LIF receptor, by adding a soluble form of the alpha CNTF receptor to the system to reconstitute the high-affinity-type CNTF receptor. The different receptor subunits were then expressed separately in transfected cells and their binding capacities analyzed. The results showed that the heterocomplex CNTF/alpha CNTF receptor bound to gp130 with an affinity of 3-5 x 10(-10)M, whereas LIF interacted mainly with gp190. In summary, the observed competition between LIF and CNTF does not result from the binding to a common site or receptor subunit, but rather to the interaction of the three receptor components to create a conformational site common to both LIF and CNTF.
authors.affiliation: Laboratoire de Biologie Cellulaire, CHU Angers, France.
authors.forename: O
authors.initials: O
authors.lastname: Robledo
authors.forename: P
authors.initials: P
authors.lastname: Auguste
authors.forename: L
authors.initials: L
authors.lastname: Coupey
authors.forename: V
authors.initials: V
authors.lastname: Praloran
authors.forename: S
authors.initials: S
authors.lastname: Chevalier
authors.forename: A
authors.initials: A
authors.lastname: Pouplard
authors.forename: H
authors.initials: H
authors.lastname: Gascan
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002522:Chlorocebus aethiops; D002822:Choriocarcinoma; D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma; D011485:Protein Binding / Q000502:physiology; D011869:Radioligand Assay; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine / Q000378:metabolism* / Q000648:ultrastructure; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism* / Q000648:ultrastructure; D053606:Receptors, OSM-LIF; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D017475:Receptors, Nerve Growth Factor; D053606:Receptors, OSM-LIF