The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine

Autor: Sylvie Chevalier, Jacques Hermann, Jean-François Gauchat, Catherine Guillet, Greg Elson, Hugues Gascan, Helene Plun-Favreau, Josy Froger, Eric Lelièvre, Odile deLapeyrière, Marie Chabbert
Rok vydání: 2001
Předmět:
Models
Molecular
STAT3 Transcription Factor
Leukemia Inhibitory Factor Receptor alpha Subunit
Receptors
OSM-LIF
Cell Survival
Recombinant Fusion Proteins
Molecular Sequence Data
Leukemia inhibitory factor receptor
Ciliary neurotrophic factor
Protein Structure
Secondary
Article
General Biochemistry
Genetics and Molecular Biology
Cell Line
Mice
Antigens
CD
Chlorocebus aethiops
Cytokine Receptor gp130
Tumor Cells
Cultured
Animals
Humans
Amino Acid Sequence
Receptors
Cytokine
Receptor
Ciliary Neurotrophic Factor
Molecular Biology
Motor Neurons
Binding Sites
Membrane Glycoproteins
General Immunology and Microbiology
biology
General Neuroscience
Cell Membrane
Oncostatin M
Glycoprotein 130
Molecular biology
DNA-Binding Proteins
COS Cells
Trans-Activators
biology.protein
Cytokines
Ciliary neurotrophic factor receptor
CLCF1
Dimerization
Leukemia inhibitory factor
Signal Transduction
Zdroj: The EMBO Journal. 20:1692-1703
ISSN: 1460-2075
DOI: 10.1093/emboj/20.7.1692
Popis: Ciliary neurotrophic factor (CNTF) is involved in the survival of a number of different neural cell types, including motor neurons. CNTF functional responses are mediated through a tripartite membrane receptor composed of two signalling receptor chains, gp130 and the leukaemia inhibitory factor receptor (LIFR), associated with a non-signalling CNTF binding receptor alpha component (CNTFR). CNTFR-deficient mice show profound neuronal deficits at birth, leading to a lethal phenotype. In contrast, inactivation of the CNTF gene leads only to a slight muscle weakness, mainly during adulthood, suggesting that CNTFR binds to a second ligand that is important for development. Modelling studies of the interleukin-6 family member cardiotrophin-like cytokine (CLC) revealed structural similarities with CNTF, including the conservation of a site I domain involved in binding to CNTFR. Co-expression of CLC and CNTFR in mammalian cells generates a secreted composite cytokine, displaying activities on cells expressing the gp130-LIFR complex on their surface. Correspondingly, CLC-CNTFR activates gp130, LIFR and STAT3 signalling components, and enhances motor neuron survival. Together, these observations demonstrate that CNTFR induces the secretion of CLC, as well as mediating the functional responses of CLC.
Databáze: OpenAIRE
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