| First Author | Garbers C | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 6 | Pages | 4346-54 |
| PubMed ID | 23209286 | Mgi Jnum | J:197111 |
| Mgi Id | MGI:5490843 | Doi | 10.1074/jbc.M112.432955 |
| Citation | Garbers C, et al. (2013) An interleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer. J Biol Chem 288(6):4346-54 |
| abstractText | IL-27 consists of the cytokine subunit p28 and the non-signaling alpha-receptor EBI3. p28 was shown to additionally act via the non-signaling membrane-bound IL-6 alpha-receptor (IL-6R) as an agonistic cytokine but also as a gp130 beta-receptor antagonist, leading to inhibition of IL-6 signaling. Here, we developed a strategy for bacterial expression, purification, and refolding of murine p28. We show that p28 did not interfere with IL-6- or IL-27-induced signaling, indicating that p28 has no antagonistic properties. Moreover, we demonstrate that murine p28 acts as an agonistic cytokine via the murine and human IL-6R, indicating that p28 exhibits no species specificity. p28 was able to induce p28-trans-signaling via the soluble IL-6R (sIL-6R), a characteristic property that was initially described for trans-signaling of IL-6 via the sIL-6R. Of notice, p28/sIL-6R trans-signaling was inhibited by the IL-6 trans-signaling antagonist, soluble gp130. At higher concentrations, p28 but not IL-6 was able to induce signaling even in the absence of IL-6R or EBI3. Although IL-27 signals via a heterodimer of the beta-receptor chains gp130 and Wsx-1, p28/IL-6R specifically recruits two gp130 beta-receptor chains for signal transduction. The binding of p28 to a gp130/Wsx-1 heterodimer or a gp130 homodimer is highly selective and controlled by a novel molecular switch induced by EBI3 or IL-6R, respectively. |
