Open Access

ARTICLE

Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling

Caroline Diveu, Anne-Hélène Lagrue Lak-Hal, Josy Froger, Elisa Ravon, Linda Grimaud, Fabien Barbier, Jacques Hermann, Hugues Gascan, Sylvie Chevalier

Inserm Unit 564, CHU d’Angers, 4 rue Larrey, 49033 Angers Cedex 01, France

* Corresponding Author: H. Gascan,

European Cytokine Network 2004, 15(4), 291-302.

Accepted 29 September 2004;

Abstract

Gp130-like receptor (GPL) is a newly identified cytokine receptor. A recent study reported the involvement of GPL, together with OSMR, in the formation of the receptor complex for IL-31, a novel immune cytokine with a skin tropism. In the present work, we analyzed the signaling properties of IL-31 in glioblastoma and melanoma tumor cells. We demonstrate that in response to IL-31, its receptor complex recruits Jak1, Jak2, STAT1, -3, -5 signaling pathways, as well as the Pi3 kinase / AKT cascade. SHP-2 and Shc adapter molecules are also recruited and contribute to an increased activation of the MAP kinase pathway in response to IL-31. Different responses were observed depending on the expression of short or long GPL receptor isoform within the studied cell lines. We show that the short form of GPL receptor exerts a profound inhibitory effect on the signaling of IL-31 and behaves as a dominant negative receptor.

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Keywords

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