ArticleThe Biochemical journal2015
PT-1 selectively activates AMPK-γ1 complexes in mouse skeletal muscle, but activates all three γ subunit complexes in cultured human cells by inhibiting the respiratory chain.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Type 2 diabetes mellitus - conventional therapies and future perspectives in innovative treatment.Biochemistry and biophysics reports · 2025Review
- Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.Journal of medicinal chemistry · 2025Review
- AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders.Drug design, development and therapy · 2025Review
- Assays of Different Mechanisms of AMPK Activation, and Use of Cells Expressing Mutant AMPK to Delineate Activation Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Review
- Impairment of Glucose Metabolism and Suppression of Stemness in MCF-7/SC Human Breast Cancer Stem Cells by Nootkatone.Pharmaceutics · 2022Article
- CARS senses cysteine deprivation to activate AMPK for cell survival.The EMBO journal · 2021Article
- Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A conserved role for AMP-activated protein kinase in NGLY1 deficiency.PLoS genetics · 2020Article
- The influence of hypoxia and energy depletion on the response of endothelial cells to the vascular disrupting agent combretastatin A-4-phosphate.Scientific reports · 2020Article
- The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport.International journal of molecular sciences · 2020Article
- AMP-activated protein kinase: the current landscape for drug development.Nature reviews. Drug discovery · 2019Review
- Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation.International journal of molecular sciences · 2018Article
- Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse.Physiological reports · 2018Article
- AMPK in skeletal muscle function and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Review
- AMPK: guardian of metabolism and mitochondrial homeostasis.Nature reviews. Molecular cell biology · 2018Review
- A Method for Rapid Screening of Anilide-Containing AMPK Modulators Based on Computational Docking and Biological Validation.Frontiers in pharmacology · 2018Article
- Novel direct AMPK activator suppresses non-small cell lung cancer through inhibition of lipid metabolism.Oncotarget · 2017Article
- Heterotypic endosomal fusion as an initial trigger for insulin-induced glucose transporter 4 (GLUT4) translocation in skeletal muscle.The Journal of physiology · 2017Article
- Mechanisms of Paradoxical Activation of AMPK by the Kinase Inhibitors SU6656 and Sorafenib.Cell chemical biology · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
AMP-activated protein kinase (AMPK) occurs as heterotrimeric complexes in which a catalytic subunit (α1/α2) is bound to one of two β subunits (β1/β2) and one of three γ subunits (γ1/γ2/γ3). The ability to selectively activate specific isoforms would be a useful research tool and a promising strategy to combat diseases such as cancer and Type 2 diabetes. We report that the AMPK activator PT-1 selectively increased the activity of γ1- but not γ3-containing complexes in incubated mouse muscle. PT-1 increased the AMPK-dependent phosphorylation of the autophagy-regulating kinase ULK1 (unc-51-like autophagy-activating kinase 1) on Ser555, but not proposed AMPK-γ3 substrates such as Ser231 on TBC1 (tre-2/USP6, BUB2, cdc16) domain family, member 1 (TBC1D1) or Ser212 on acetyl-CoA carboxylase subunit 2 (ACC2), nor did it stimulate glucose transport. Surprisingly, however, in human embryonic kidney (HEK) 293 cells expressing human γ1, γ2 or γ3, PT-1 activated all three complexes equally. We were unable to reproduce previous findings suggesting that PT-1 activates AMPK by direct binding between the kinase and auto-inhibitory domains (AIDs) of the α subunit. We show instead that PT-1 activates AMPK indirectly by inhibiting the respiratory chain and increasing cellular AMP:ATP and/or ADP:ATP ratios. Consistent with this mechanism, PT-1 failed to activate AMPK in HEK293 cells expressing an AMP-insensitive R299G mutant of AMPK-γ1. We propose that the failure of PT-1 to activate γ3-containing complexes in muscle is not an intrinsic feature of such complexes, but is because PT-1 does not increase cellular AMP:ATP ratios in the specific subcellular compartment(s) in which γ3 complexes are located.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.