Interleukin-6 signal transducer gp130 mediates oncostatin M signaling.
Oncostatin M (OM) is a multifunctional cytokine that is structurally and functionally related to interleukin 6 (IL-6) and leukemia inhibitory factor (LIF). The specific receptor for OM has been demonstrated (by chemical cross-linking) to be a 150-kDa protein in a number of cell lines. The IL-6 signal transducer, gp130, is also an affinity converter for the LIF receptor. It does not bind to either IL-6 or LIF, but associates with the alpha subunits of the receptors and transduces the signals. We examined the possible involvement of gp130 in OM binding and signaling. We demonstrate that: (a) anti-gp130 monoclonal antibodies (mAbs) block the inhibitory effect of OM on A375 cell growth, (b) the binding and cross-linking of 125I-OM to H2981 cells are completely abolished by anti-gp130 mAbs, (c) the cross-linked OM-receptor complex is immunoprecipitated by anti-gp130 mAbs, and (d) COS-7 cells transfected with the full-length cDNA encoding gp130 exhibit increased OM binding and cross-linking, which are also blocked by anti-gp130 mAbs. Therefore, we conclude that the 150-kDa OM binding protein previously characterized in a variety of cell lines is gp130. OM is the natural ligand for gp130 and gp130 mediates the biological responses of OM.
Liu
J
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Modrell
B
B
Aruffo
A
A
Marken
J S
JS
Taga
T
T
Yasukawa
K
K
Murakami
M
M
Kishimoto
T
T
Shoyab
M
M
D000818:Animals; D015703:Antigens, CD; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003432:Cross-Linking Reagents; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008545:Melanoma; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D003432:Cross-Linking Reagents; D016207:Cytokines; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D050822:Cytokine Receptor gp130