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  2. Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor component

Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor component

  • J Biol Chem. 1997 Feb 21;272(8):4855-63. doi: 10.1074/jbc.272.8.4855.
O Robledo 1 M Fourcin S Chevalier C Guillet P Auguste A Pouplard-Barthelaix D Pennica H Gascan
Affiliations

Affiliation

  • 1 Laboratoire de Biologie Cellulaire, 4 rue Larrey, CHU Angers, 49033 Angers Cedex, France.
Abstract

Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to the interleukin-6 cytokine family. In the present study we show that CT-1 activates its receptor expressed at the surface of a human neural cell line by recruiting gp130 and gp190/Leukemia Inhibitory Factor receptor beta, as shown by analyzing their tyrosine phosphorylation level. Neutralizing antibody directed against gp130 and reconstitution experiments performed in the COS-7 cell line demonstrate that gp130-gp190 heterocomplex formation is essential for CT-1 signaling. Analysis of the subsequent activation events revealed that CT-1 induces and utilizes Jak1-, Jak2-, and Tyk2-associated tyrosine kinases, which are in turn relayed by STAT-3 transcription factor. Cross-linking of iodinated CT-1 to the cell surface led to the identification of a third alpha component in addition to gp130 and gp190, with an apparent molecular mass of 80 kDa. Removal of N-linked Carbohydrates from the protein backbone of the alpha component resulted in a protein of 45 kDa. Our results provide evidence that the CT-1 receptor is composed of a tripartite complex, a situation similar to the high affinity receptor for ciliary neurotrophic factor.

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