| First Author | Shen M | Year | 2011 |
| Journal | Exp Cell Res | Volume | 317 |
| Issue | 7 | Pages | 976-93 |
| PubMed ID | 21182835 | Mgi Jnum | J:172699 |
| Mgi Id | MGI:5008547 | Doi | 10.1016/j.yexcr.2010.12.012 |
| Citation | Shen M, et al. (2011) Diverse functions of reactive cysteines facilitate unique biosynthetic processes of aggregate-prone interleukin-31. Exp Cell Res 317(7):976-93 |
| abstractText | Interleukin-31 (IL-31) is a member of the four helical-bundle gp130/IL-6 cytokine family. Despite its implicated roles in inflammatory diseases, the biosynthetic processes of IL-31 have been poorly investigated. A detailed understanding of IL-31 biosynthesis and the nature of ligand-receptor interactions can provide insights into effective strategies for the design of therapeutic approaches. By using various heterologous protein expression systems, we demonstrated that murine IL-31 was secreted as inter-molecularly disulfide-bonded covalent aggregates. Covalently aggregated IL-31 appeared while trafficking in the secretory pathway, but was not actively retained in the ER. The aggregate formation was not caused by a dysfunctional ER quality control mechanism or an intrinsic limitation in protein folding capacity. Furthermore, secreted IL-31 aggregates were part of a large complex composed of various pleiotropic secretory factors and immune-stimulators. The extent and the heterogeneous nature of aggregates may imply that IL-31 was erroneously folded, but it was capable of signaling through cognate receptors. Mutagenesis revealed the promiscuity of all five cysteines in inter-molecular disulfide formation with components of the hetero-aggregates, but no cysteine was required for IL-31 secretion itself. Our present study not only illustrated various functions that cysteines perform during IL-31 biosynthesis and secretion, but also highlighted their potential roles in cytokine effector functions. |
