Membrane distal cytokine binding domain of LIFR interacts with soluble CNTFR in vitro.
Ciliary neurotrophic factor (CNTF) is a member of the gp130 family of cytokines. The functional receptor complex of CNTF is composed of the CNTF receptor alpha (CNTFR), gp130 and the leukemia inhibitory factor receptor (LIFR). Three regions on CNTF have been identified as binding sites for its receptors. The ligand-receptor interactions are mediated through the cytokine binding domains (CBDs) and/or the immunoglobulin-like domains of the receptors. However, in the case of CNTF, the precise nature of the protein-protein contacts in the signaling complex has not yet been resolved. In this study, we provide the first demonstration that the membrane distal CBD (CBD1) of LIFR associates in vitro with soluble CNTFR in the absence of CNTF. Moreover, purified CBD1 partially blocks CNTF signaling, but not that of interleukin-6 or LIF, in human embryonal carcinoma cell line Ntera/D1 cells. These data raise the possibility that LIFR has the capability to form a ligand-free complex with CNTFR.
He
Wei
W
Department of Biochemistry and Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, PR China.
Gong
Ke
K
Zhu
Guang
G
Smith
David K
DK
Ip
Nancy Y
NY
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells; D004797:Enzyme-Linked Immunosorbent Assay; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000494:pharmacology; D046911:Macromolecular Substances; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; 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; C507842:Lifr protein, rat; D008222:Lymphokines; D046911:Macromolecular Substances; D010446:Peptide Fragments; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D011993:Recombinant Fusion Proteins