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Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5

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 ide...

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Autores principales: Yan, Yi, Tsukamoto, Osamu, Nakano, Atsushi, Kato, Hisakazu, Kioka, Hidetaka, Ito, Noriaki, Higo, Shuichiro, Yamazaki, Satoru, Shintani, Yasunori, Matsuoka, Ken, Liao, Yulin, Asanuma, Hiroshi, Asakura, Masanori, Takafuji, Kazuaki, Minamino, Tetsuo, Asano, Yoshihiro, Kitakaze, Masafumi, Takashima, Seiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317497/
https://www.ncbi.nlm.nih.gov/pubmed/25635515
http://dx.doi.org/10.1038/ncomms7137
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author Yan, Yi
Tsukamoto, Osamu
Nakano, Atsushi
Kato, Hisakazu
Kioka, Hidetaka
Ito, Noriaki
Higo, Shuichiro
Yamazaki, Satoru
Shintani, Yasunori
Matsuoka, Ken
Liao, Yulin
Asanuma, Hiroshi
Asakura, Masanori
Takafuji, Kazuaki
Minamino, Tetsuo
Asano, Yoshihiro
Kitakaze, Masafumi
Takashima, Seiji
author_facet Yan, Yi
Tsukamoto, Osamu
Nakano, Atsushi
Kato, Hisakazu
Kioka, Hidetaka
Ito, Noriaki
Higo, Shuichiro
Yamazaki, Satoru
Shintani, Yasunori
Matsuoka, Ken
Liao, Yulin
Asanuma, Hiroshi
Asakura, Masanori
Takafuji, Kazuaki
Minamino, Tetsuo
Asano, Yoshihiro
Kitakaze, Masafumi
Takashima, Seiji
author_sort Yan, Yi
collection PubMed
description 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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spelling pubmed-43174972015-02-17 Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5 Yan, Yi Tsukamoto, Osamu Nakano, Atsushi Kato, Hisakazu Kioka, Hidetaka Ito, Noriaki Higo, Shuichiro Yamazaki, Satoru Shintani, Yasunori Matsuoka, Ken Liao, Yulin Asanuma, Hiroshi Asakura, Masanori Takafuji, Kazuaki Minamino, Tetsuo Asano, Yoshihiro Kitakaze, Masafumi Takashima, Seiji Nat Commun Article 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. Nature Pub. Group 2015-01-30 /pmc/articles/PMC4317497/ /pubmed/25635515 http://dx.doi.org/10.1038/ncomms7137 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Yan, Yi
Tsukamoto, Osamu
Nakano, Atsushi
Kato, Hisakazu
Kioka, Hidetaka
Ito, Noriaki
Higo, Shuichiro
Yamazaki, Satoru
Shintani, Yasunori
Matsuoka, Ken
Liao, Yulin
Asanuma, Hiroshi
Asakura, Masanori
Takafuji, Kazuaki
Minamino, Tetsuo
Asano, Yoshihiro
Kitakaze, Masafumi
Takashima, Seiji
Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
title Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
title_full Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
title_fullStr Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
title_full_unstemmed Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
title_short Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
title_sort augmented ampk activity inhibits cell migration by phosphorylating the novel substrate pdlim5
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317497/
https://www.ncbi.nlm.nih.gov/pubmed/25635515
http://dx.doi.org/10.1038/ncomms7137
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