| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Ba/F3(RCB0805) |
