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

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.

Aplysia kurodai -derived glycosaminoglycans increase the phagocytic ability of macrophages via the activation of AMP-activated protein kinase and cytoskeletal reorganization in RAW264.7 cells

“…GAG is structurally similar to LPS and is involved in pathogenesis of inflammation through LPS signalling pathways (Simonaro et al, 2008). Numerous studies demonstrated that the AMPK activator AICAR enhances the phagocytic ability of macrophages via a variety of signalling events, and AMPK activation induces cytoskeletal reorganization (Bae et al, 2011;Yan et al, 2015). Consistent with earlier studies, our results showed that AICAR increased the phagocytic ability of macrophages.…”

Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

“…Furthermore, we validated the expression of genes at the core nodes of the circRNA-miRNA-mRNA regulatory network by qPCR. PDLIM5, which was upregulated in TDP cells, functions as an oncogene in cancer by promoting cell proliferation and migration [27,28]. Moreover, miR-328, which interacts with PDLIM5, has Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry been found downregulated in multiple cancers.…”

AMPK Inhibits the Stimulatory Effects of TGF-βon Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition

“…In addition, AMPK inhibits cancer cell migration and EMT via both TGF-b-dependent and -independent mechanisms (Cufi et al, 2010;Xiao et al, 2010;Lim et al, 2012;Chou et al, 2014;Wang et al, 2014;Zhang et al, 2014;Thakur et al, 2015;Yan et al, 2015). With regard to AMPK regulation of the TGF-b signaling pathway, the mechanism is not clear.…”