論文 - 詳細
| RRC ID | 38210 |
|---|---|
| 著者 | Shindo Y, Iwamoto K, Mouri K, Hibino K, Tomita M, Kosako H, Sako Y, Takahashi K. |
| タイトル | Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling. |
| ジャーナル | Nat Commun |
| Abstract |
The phosphorylation cascade in the extracellular signal-regulated kinase (ERK) pathway is a versatile reaction network motif that can potentially act as a switch, oscillator or memory. Nevertheless, there is accumulating evidence that the phosphorylation response is mostly linear to extracellular signals in mammalian cells. Here we find that subsequent nuclear translocation gives rise to a switch-like increase in nuclear ERK concentration in response to signal input. The switch-like response disappears in the presence of ERK inhibitor, suggesting the existence of autoregulatory mechanisms for ERK nuclear translocation involved in conversion from a graded to a switch-like response. In vitro reconstruction of ERK nuclear translocation indicates that ERK-mediated phosphorylation of nucleoporins regulates ERK translocation. A mathematical model and knockdown experiments suggest a contribution of nucleoporins to regulation of the ERK nuclear translocation response. Taken together, this study provides evidence that nuclear translocation with autoregulatory mechanisms acts as a switch in ERK signalling. |
| 巻・号 | 7 |
| ページ | 10485 |
| 公開日 | 2016-1-20 |
| DOI | 10.1038/ncomms10485 |
| PII | ncomms10485 |
| PMID | 26786866 |
| PMC | PMC4736105 |
| MeSH | Animals Cell Nucleus / metabolism* Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism* Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism PC12 Cells Phosphorylation / genetics Phosphorylation / physiology Protein Transport / genetics Protein Transport / physiology RNA Interference Rats |
| IF | 12.121 |
| 引用数 | 28 |
| WOS 分野 | CELL BIOLOGY |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 17 |
| 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 | |
| 遺伝子材料 | pGEX-GFP-ERK2-His (RDB14152) pCMV-GFP-ERK2 (RDB14156) pACYC184-Venus-MEK1 (S218/222E delta32-51) (RDB14154). |
| ヒト・動物細胞 | PC-12(RCB0009) |