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PMID:10966616

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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

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

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

HUMAN:CNTF

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:CNTF

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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