論文 - 詳細
| RRC ID | 34853 |
|---|---|
| 著者 | Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S. |
| タイトル | Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5. |
| ジャーナル | Nat Commun |
| Abstract |
Augmented AMP-activated protein kinase (AMPK) activity inhibits cell migration, possibly contributing to the clinical benefits of chemical AMPK activators in preventing atherosclerosis, vascular remodelling and cancer metastasis. However, the underlying mechanisms remain largely unknown. Here we identify PDZ and LIM domain 5 (Pdlim5) as a novel AMPK substrate and show that it plays a critical role in the inhibition of cell migration. AMPK directly phosphorylates Pdlim5 at Ser177. Exogenous expression of phosphomimetic S177D-Pdlim5 inhibits cell migration and attenuates lamellipodia formation. Consistent with this observation, S177D-Pdlim5 suppresses Rac1 activity at the cell periphery and displaces the Arp2/3 complex from the leading edge. Notably, S177D-Pdlim5, but not WT-Pdlim5, attenuates the association with Rac1-specific guanine nucleotide exchange factors at the cell periphery. Taken together, our findings indicate that phosphorylation of Pdlim5 on Ser177 by AMPK mediates inhibition of cell migration by suppressing the Rac1-Arp2/3 signalling pathway. |
| 巻・号 | 6 |
| ページ | 6137 |
| 公開日 | 2015-1-30 |
| DOI | 10.1038/ncomms7137 |
| PII | ncomms7137 |
| PMID | 25635515 |
| PMC | PMC4317497 |
| MeSH | AMP-Activated Protein Kinases / metabolism* Actin-Related Protein 2-3 Complex / metabolism Adaptor Proteins, Signal Transducing / metabolism* Animals Cell Line Cell Movement / physiology Mice Microfilament Proteins / metabolism* Phosphorylation Signal Transduction / physiology rac1 GTP-Binding Protein / metabolism |
| IF | 12.121 |
| 引用数 | 40 |
| 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
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 6 |
| 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 | pEF-DEST51_mm Pdlim5 (RDB13418) pEF-DEST51_mm S177A Pdlim5 (RDB13419) pEF-DEST51_mm S177D Pdlim5 (RDB13420) pGEX6.1_mm Pdlim5 (RDB13421) pGEX6.1_mm S177A Pdlim5 (RDB13422) pGEX6.1_mm S177D Pdlim5 (RDB13423). |