期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7137
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资金
- Japan Society for the Promotion of Science (JSPS) through the Funding Program for Next-Generation World-Leading Researchers (NEXT Program)
- Ministry of Health, Labour and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science
- Japan Heart Foundation
- Japan Cardiovascular Research Foundation
- Japan Medical Association
- Japan Intractable Diseases Research Foundation
- Uehara Memorial Foundation
- Takeda Science Foundation
- Ichiro Kanehara Foundation
- Inoue Foundation for Science
- Mochida Memorial Foundation
- Heart Foundation/Novartis Grant for Research Award on Molecular and Cellular Cardiology
- Japan Foundation of Applied Enzymology
- Naito Foundation
- Banyu Foundation and Showa Houkoukai
- Grants-in-Aid for Scientific Research [25461119, 26860558, 24591096, 26461108] Funding Source: KAKEN
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.
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