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CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex.

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.

Pubmed ID: 10966616

Authors

  • Elson GC
  • Lelièvre E
  • Guillet C
  • Chevalier S
  • Plun-Favreau H
  • Froger J
  • Suard I
  • de Coignac AB
  • Delneste Y
  • Bonnefoy JY
  • Gauchat JF
  • Gascan H

Journal

Nature neuroscience

Publication Data

September 28, 2000

Associated Grants

None

Mesh Terms

  • Animals
  • COS Cells
  • Cell Differentiation
  • Cell Survival
  • Cytokines
  • Ligands
  • Motor Neurons
  • Nerve Degeneration
  • Radioligand Assay
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Cytokine
  • Tumor Cells, Cultured