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PMID:10966616
Citation |
Elson, GC, Lelièvre, E, Guillet, C, Chevalier, S, Plun-Favreau, H, Froger, J, Suard, I, de Coignac, AB, Delneste, Y, Bonnefoy, JY, Gauchat, JF and Gascan, H (2000) CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat. Neurosci. 3:867-72 |
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Abstract |
Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second, developmentally important ligand. We have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF expression was required for CLC secretion, and the complex acted only on cells expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR and signal transducer and activator of transcription 3 (STAT3) and supported motor neuron survival. Our results indicate that the CLF/CLC complex is a second ligand for CNTFR with potentially important implications in nervous system development. |
Links |
PubMed Online version:10.1038/78765 |
Keywords |
Animals; COS Cells; Cell Differentiation/physiology; Cell Survival/physiology; Cytokines/metabolism; Cytokines/secretion; Ligands; Motor Neurons/cytology; Motor Neurons/metabolism; Nerve Degeneration/physiopathology; Radioligand Assay; Receptor, Ciliary Neurotrophic Factor/metabolism; Receptors, Cytokine/metabolism; Tumor Cells, Cultured |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
HUMAN:CRLF1 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q9UBD9 |
F |
Seeded From UniProt |
complete | |
HUMAN:CRLF1 |
part_of |
GO:0097058: CRLF-CLCF1 complex |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
HUMAN:CRLF1 |
involved_in |
GO:0008284: positive regulation of cell population proliferation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:CRLF1 |
contributes_to |
GO:0005125: cytokine activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
HUMAN:CRLF1 |
contributes_to |
GO:0005127: ciliary neurotrophic factor receptor binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
HUMAN:CRLF1 |
involved_in |
GO:0043524: negative regulation of neuron apoptotic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:CRLF1 |
involved_in |
GO:0042531: positive regulation of tyrosine phosphorylation of STAT protein |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O75462 |
F |
Seeded From UniProt |
complete | |
HUMAN:CLCF1 |
part_of |
GO:0097058: CRLF-CLCF1 complex |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
located_in |
GO:0005576: extracellular region |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
involved_in |
GO:0008284: positive regulation of cell population proliferation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
contributes_to |
GO:0005125: cytokine activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
contributes_to |
GO:0005127: ciliary neurotrophic factor receptor binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
involved_in |
GO:0043524: negative regulation of neuron apoptotic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:CLCF1 |
involved_in |
GO:0042531: positive regulation of tyrosine phosphorylation of STAT protein |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
involved_in |
GO:0043524: negative regulation of neuron apoptotic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
enables |
GO:0044877: protein-containing complex binding |
ECO:0000353: physical interaction evidence used in manual assertion |
GO:0097058 |
F |
Seeded From UniProt |
complete | ||
See also
References
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