ArticleThe Journal of biological chemistry2015
Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2APpp2r2d.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
- Protein phosphatase 2A impairs cardiac uptake of glucose in the mammalian heart.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Translational control of AMPK activity in melanoma.Cell communication and signaling : CCS · 2026Article
- Elevated Kallistatin Induces Myosteatosis and Exercise Intolerance by Antagonizing AdipoR1-Mediated AMPK Signalling.Journal of cachexia, sarcopenia and muscle · 2026Article
- Transcriptional control of PPP2CB by YAP1 and TEAD1 mediates AMPK inhibition and mTORC1 activation in vascular smooth muscle cells.iScience · 2026Article
- Microcystin-LR Drives Early NAFLD Pathogenesis via Hepatic Cholesterol Accumulation: Dysregulation ofToxins · 2026Article
- The inhibitory SAPS3-AMPK interaction detected in HEK293 cells is not detectable in muscle or liver from humans or mice.FEBS letters · 2025Article
- AMPK phosphorylates WIP1 to promote DNA repair and radioresistance in cancer cells.Cell death & disease · 2025Article
- Cytosolic DNA and intracellular CaDNA repair · 2025Review
- Article
- Sephin1 suppresses ER stress-induced cell death by inhibiting the formation of PP2A holoenzyme.Cell death & disease · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Bioenergetic adaptations of small intestinal epithelial cells reduce cell differentiation enhancing intestinal permeability in obese mice.Molecular metabolism · 2025Article
- Suppression of neuronal AMPKβ2 isoform impairs recognition memory and synaptic plasticity.Neurobiology of disease · 2024Article
- Role of the AMP-Activated Protein Kinase in the Pathogenesis of Polycystic Ovary Syndrome.Indian journal of clinical biochemistry : IJCB · 2024Review
- AMPK as a mediator of tissue preservation: time for a shift in dogma?Nature reviews. Endocrinology · 2024Review
- Resveratrol Induces Myotube Development by Altering Circadian Metabolism via the SIRT1-AMPK-PP2A Axis.Cells · 2024Article
- Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer.Genes & diseases · 2024Article
- MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D.BMJ open diabetes research & care · 2024Article
- Overexpression of AMPKγ2 increases AMPK signaling to augment human T cell metabolism and function.The Journal of biological chemistry · 2024Article
- Inhibition of WNK Kinases in NK Cells Disrupts Cellular Osmoregulation and Control of Tumor Metastasis.Journal of innate immunity · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive. Here we discovered that the protein phosphatase 2A heterotrimer, PP2A(Ppp2r2d), regulates the phosphorylation state of AMP kinase by dephosphorylating Thr-172, a residue that activates kinase activity when phosphorylated. Co-immunoprecipitation and co-localization studies indicated that PP2A(Ppp2r2d) directly interacted with AMP kinase. PP2A(Ppp2r2d) dephosphorylated Thr-172 in rat aortic and human vascular smooth muscle cells. A positive correlation existed between decreased phosphorylation, decreased acetyl-CoA carboxylase Acc1 phosphorylation, and sterol response element-binding protein 1c-dependent gene expression. PP2A(Ppp2r2d) protein expression was up-regulated in the aortas of mice fed a high fat diet, and the increased expression correlated with increased blood lipid levels. Finally, we found that the aortas of mice fed a high fat diet had decreased AMP kinase Thr-172 phosphorylation, and contained an Ampk-PP2A(Ppp2r2d) complex. Thus, PP2A(Ppp2r2d) may antagonize the aortic AMP kinase activity necessary for maintaining normal aortic lipid metabolism. Inhibiting PP2A(Ppp2r2d) or activating AMP kinase represents a potential pharmacological treatment for many lipid-related diseases.
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