Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling.
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.
Diveu
Caroline
C
Inserm Unit 564, CHU d'Angers, 4 rue Larrey, 49033 Angers Cedex 01, France.
Lak-Hal
Anne-Hélène Lagrue
AH
Froger
Josy
J
Ravon
Elisa
E
Grimaud
Linda
L
Barbier
Fabien
F
Hermann
Jacques
J
Gascan
Hugues
H
Chevalier
Sylvie
S
D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology; D018121:Receptors, Cytokine / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; D020033:Protein Isoforms; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; C456339:cytokine receptor, GLM-R