The regulation of AMP-activated protein kinase by phosphorylation

Stein, Silvie C.; Woods, Angela; Jones, Nick D.; Davison, Matt; Carling, David

doi:10.1042/bj3450437

Cited by 473 publications

(233 citation statements)

References 30 publications

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“…AMPK activation can acutely regulate metabolism as well as chronically alter gene expression to the same effect. High cellular concentrations of ATP antagonize the effects of AMP on AMPK so that AMPK responds sensitively to the AMP-to-ATP ratio [4,6,8,17,19,20,22,23,27,28,34,41]. In the present study, we establish the presence of AMPK in the mitochondrion-rich, particularly ATP-dependent, parietal cell.…”

Section: Introductionsupporting

confidence: 51%

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion

Sidani

Kopic

Socrates

et al. 2009

Pflugers Arch - Eur J Physiol

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Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-beta-D: -riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion.

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Section: Introductionsupporting

confidence: 51%

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion

Sidani

Kopic

Socrates

et al. 2009

Pflugers Arch - Eur J Physiol

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“…In this in vivo model, ATP appeared to play a minor role in antagonism of the AMP-activation effect. Activation of AMPK by AMP in vitro is markedly inhibited by 4 mM ATP [170]. The NMR data suggest that the total ATP in heart is not accessible to AMPK, or possibly in the cellular environment, the enzyme is less sensitive to the ATP inhibitory effect observed in vitro.…”

Section: How Is It Activated?mentioning

confidence: 84%

Cellular energy sensing and signaling by AMP-activated protein kinase

Winder

Thomson

2007

Cell Biochem Biophys

131

123

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AMP-activated protein kinase (AMPK) is an energy sensing/signaling protein that, when activated, increases ATP production by stimulating glucose uptake and fatty acid oxidation while at the same time inhibiting ATP = consuming processes such as protein synthesis. Chronic activation of AMPK inhibits expression of lipogenic enzymes in the liver and enhances expression of mitochondrial oxidative enzymes in skeletal muscle. Deficiency of muscle LKB1, the upstream kinase of AMPK, results in greater fluctuation in energy charge during muscle contraction and decreased capacity for exercise at higher work rates. Because AMPK enhances both glucose uptake and fatty acid oxidation in skeletal muscle, it has become a target for prevention and treatment of type 2 diabetes and obesity.

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“…[U-14 C]-glucose was from GE healthcare (Diegem, Belgium). Expression plasmids (pcDNA3, Invitrogen) encoding AMPKa1, AMPKb1 and AMPKg1 were provided by Dr. D. Carling [12].…”

Section: Methodsmentioning

confidence: 99%

Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids

Houten

Chegary

Brinke

et al. 2009

Cell. Mol. Life Sci.

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Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status in order to spare glucose.

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The regulation of AMP-activated protein kinase by phosphorylation

Cited by 473 publications

References 30 publications

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion

Cellular energy sensing and signaling by AMP-activated protein kinase

Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids

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