Molecular and functional characterization of a soluble form of oncostatin M/interleukin-31 shared receptor.
Activation of the signaling transduction pathways mediated by oncostatin M (OSM) requires the binding of the cytokine to either type I OSM receptor (leukemia inhibitory factor receptor/gp130) or to type II OSM receptor (OSMR/gp130). In the present work we have developed an enzyme-linked immunosorbent assay detecting a soluble form of OSMR (sOSMR) secreted by glioblastoma, hepatoma, and melanoma tumor cell lines. sOSMR was also present in sera of healthy individuals, with increased levels in multiple myeloma. Molecular cloning of a corresponding cDNA was carried out, and it encoded for a 70-kDa protein consisting of a half cytokine binding domain containing the canonical WSXWS motif, an immunoglobulin-like domain, and the first half of a second cytokine binding domain with cysteines in fixed positions. Analysis of the soluble receptor distribution revealed a preferential expression in lung, liver, pancreas, and placenta. sOSMR was able to bind OSM and interleukin-31 when associated to soluble gp130 or soluble interleukin-31R, respectively, and to neutralize both cytokine properties. We have also shown that OSM could positively regulate the synthesis of its own soluble receptor in tumor cells.
Diveu
Caroline
C
Institut National de la Santé et de la Recherche Médicale, U564, F-49033 Angers, France.
Venereau
Emilie
E
Froger
Josy
J
Ravon
Elisa
E
Grimaud
Linda
L
Rousseau
François
F
Chevalier
Sylvie
S
Gascan
Hugues
H
D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130 / Q000737:chemistry / Q000502:physiology*; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D053683:Oncostatin M / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053606:Receptors, OSM-LIF / Q000737:chemistry / Q000502:physiology*; D014018:Tissue Distribution
C502187:IL31 protein, human; C494199:IL6ST protein, human; D007378:Interleukins; D053606:Receptors, OSM-LIF; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D006026:Glycoside Hydrolases