Oncostatin M binds directly to gp130 and behaves as interleukin-6 antagonist on a cell line expressing gp130 but lacking functional oncostatin M receptors

Elisabetta Sporeno, Giacomo Paonessa, Anna Laura Salvati, Rita Graziani, Paolo Delmastro, Gennaro Ciliberto, Carlo Toniatti

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Abstract

Oncostatin M (OM) and interleukin 6 (IL-6) are functionally related cytokines, which trigger similar biological responses because they share gp130 as a common signal transducing transmembrane receptor. While IL-6 recruits gp130 only upon binding to its specific receptor subunit (IL-6Rα), reconstitution and cross-linking experiments on cell membranes suggest that OM can directly interact with gp130 and that this interaction is necessary but not sufficient to stimulate cells. However, the issue of the direct binding between gp130 and OM, in the absence of any additional membrane component, remained essentially unclarified. In this paper we show that, uniquely among the family of cytokines that transduce through gp130, OM directly binds in vitro with a 10-8 M affinity sgp130, a soluble form of gp130. Moreover, titration of sgp130 with OM inhibits the formation of a ternary complex comprising IL-6, sIL-6Rα, and sgp130. These in vitro properties of OM are consistent with the additional finding that on human hepatoma Hep3B cells, which express gp130 but not functional OM receptors, OM does not mimic IL-6 activity, but rather behaves, at high doses, as an IL-6 antagonist.

Original languageEnglish
Pages (from-to)10991-10995
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number15
Publication statusPublished - Apr 15 1994

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Oncostatin M Receptors
Oncostatin M
Cytokine Receptor gp130
Interleukin-6
Cells
Cell Line
Cytokines
Cell membranes
Titration
Hepatocellular Carcinoma
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Oncostatin M binds directly to gp130 and behaves as interleukin-6 antagonist on a cell line expressing gp130 but lacking functional oncostatin M receptors. / Sporeno, Elisabetta; Paonessa, Giacomo; Salvati, Anna Laura; Graziani, Rita; Delmastro, Paolo; Ciliberto, Gennaro; Toniatti, Carlo.

In: Journal of Biological Chemistry, Vol. 269, No. 15, 15.04.1994, p. 10991-10995.

Research output: Contribution to journalArticle

Sporeno, Elisabetta ; Paonessa, Giacomo ; Salvati, Anna Laura ; Graziani, Rita ; Delmastro, Paolo ; Ciliberto, Gennaro ; Toniatti, Carlo. / Oncostatin M binds directly to gp130 and behaves as interleukin-6 antagonist on a cell line expressing gp130 but lacking functional oncostatin M receptors. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 15. pp. 10991-10995.
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