論文 - 詳細
| RRC ID | 68648 |
|---|---|
| 著者 | Shen M, Siu S, Byrd S, Edelmann KH, Patel N, Ketchem RR, Mehlin C, Arnett HA, Hasegawa H. |
| タイトル | Diverse functions of reactive cysteines facilitate unique biosynthetic processes of aggregate-prone interleukin-31. |
| ジャーナル | Exp Cell Res |
| Abstract |
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. |
| 巻・号 | 317(7) |
| ページ | 976-93 |
| 公開日 | 2011-4-15 |
| DOI | 10.1016/j.yexcr.2010.12.012 |
| PII | S0014-4827(10)00570-7 |
| PMID | 21182835 |
| MeSH | Animals Cell Line Cell Proliferation Cysteine / metabolism* Endoplasmic Reticulum / metabolism Golgi Apparatus / metabolism HEK293 Cells Humans Inclusion Bodies / chemistry* Interleukins / biosynthesis* Interleukins / genetics Mice Protein Processing, Post-Translational Signal Transduction / physiology |
| IF | 3.383 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Ba/F3(RCB0805) |