Graduate School of Frontier Biosciences, Osaka University

Japanese

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

Journal Nat Commun 30, 6137 (2015)
Authors Yan Y. (1), Tsukamoto O. (1), Nakano A. (2), Kato H. (1), Kioka H. (3), Ito N. (3), Higo S. (3), Yamazaki S. (4), Shintani Y. (1), Matsuoka K. (3), Liao Y. (5), Asanuma H. (2), Asakura M. (2), Takafuji K. (6), Minamino T. (3), Asano Y. (3), Kitakaze M. (2), Takashima S. (7, 8)

  1. Department of Medical Biochemistry, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  2. Depertment of Clinical Research and Development, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan
  3. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  4. Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan
  5. Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, 510515 Guangzhou, China
  6. Center for Research Education, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  7. Department of Medical Biochemistry, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  8. Japan Science and Technology Agency-Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012, Japan
Title Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5.
PubMed 25635515
Laboratory Department of Medical Biochemistry 〈Prof. Takashima〉
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.