scholarly journals Sumoylation of AMPKβ2 subunit enhances AMP-activated protein kinase activity

2013 ◽  
Vol 24 (11) ◽  
pp. 1801-1811 ◽  
Author(s):  
Teresa Rubio ◽  
Santiago Vernia ◽  
Pascual Sanz
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Catalytic Domain ◽  
Protein Kinase Activity ◽  
Energy Status ◽  
Regulatory Subunits ◽  
Cellular Energy ◽  
Sumo Ligase ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is a heterotrimer composed of a catalytic α and two regulatory subunits (β and γ). AMPK activity is regulated allosterically by AMP and by the phosphorylation of residue Thr-172 within the catalytic domain of the AMPKα subunit by upstream kinases. We present evidence that the AMPKβ2 subunit may be posttranslationally modified by sumoylation. This process is carried out by the E3-small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated STAT PIASy, which modifies the AMPKβ2 subunit by the attachment of SUMO2 but not SUMO1 moieties. Of interest, AMPKβ1 is not a substrate for this modification. We also demonstrate that sumoylation of AMPKβ2 enhances the activity of the trimeric α2β2γ1 AMPK complex. In addition, our results indicate that sumoylation is antagonist and competes with the ubiquitination of the AMPKβ2 subunit. This adds a new layer of complexity to the regulation of the activity of the AMPK complex, since conditions that promote ubiquitination result in inactivation, whereas those that promote sumoylation result in the activation of the AMPK complex.

scholarly journals Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

2007 ◽  
Vol 192 (3) ◽  
pp. 605-614 ◽  
Author(s):  
Fang Cai ◽  
Armen V Gyulkhandanyan ◽  
Michael B Wheeler ◽  
Denise D Belsham
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Cell Model ◽  
Neuronal Cell ◽  
Cell Types ◽  
Glucose Sensing ◽  
Protein Kinase Activity ◽  
Energy Status ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

scholarly journals ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise

2019 ◽  
Author(s):  
Ian F. Coccimiglio ◽  
David C. Clarke
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Adenine Nucleotides ◽  
Protein Kinase Activity ◽  
Global Parameter ◽  
Cellular Energy ◽  
Direct Binding ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Activity Dynamics

AbstractExercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that AMPK activity dynamics are determined principally by ADP and not AMP. We then used the model to predict the effects of two additional direct-binding activators of AMPK, ZMP and Compound 991, further validating the model and demonstrating its applicability to understanding AMPK pharmacology. The relative effects of direct-binding activators can be understood in terms of four properties, namely their concentrations, binding affinities for AMPK, abilities to enhance AMPK phosphorylation, and the magnitudes of their allosteric activation of AMPK. Despite AMP’s favorable values in three of these four properties, ADP is the dominant controller of AMPK activity dynamics in skeletal muscle during exercise by virtue of its higher concentration.Author SummaryDuring exercise, the enzyme “AMP-activated protein kinase” (AMPK) detects the disrupted cellular energy state by binding to the adenine nucleotides ATP, ADP, and AMP, which are the major chemical energy carriers of the cell. How the adenine nucleotides interact to control AMPK activity is poorly understood. In this study, we used mathematical modeling to investigate the control of AMPK activity by the adenine nucleotides in skeletal muscle during exercise. We simulated the model many times with randomly generated parameter sets. Ultimately the parameters affect four key properties of an AMPK activator, namely its concentration, the tightness with which it binds to AMPK, its ability to activate AMPK by promoting its phosphorylation, and its ability to activate AMPK through allostery. We found that ADP is the dominant controller of AMPK activity, instead of AMP, due to its high concentration relative to that of AMP. We also modeled AMPK activity in response to drugs that activate it, which further demonstrated the validity and applicability of the model. Overall, our research enhances understanding of AMPK action during exercise and could inform the development of drugs that target AMPK.

scholarly journals 5′-AMP-activated protein kinase activity is elevated early during primary brain tumor development in the rat

2010 ◽  
Vol 128 (9) ◽  
pp. 2230-2239 ◽  
Author(s):  
Taichang Jang ◽  
Joy M. Calaoagan ◽  
Eunice Kwon ◽  
Steven Samuelsson ◽  
Lawrence Recht ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Tumor Development ◽  
Primary Brain Tumor ◽  
Protein Kinase Activity ◽  
Amp Activated Protein Kinase

scholarly journals Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

2007 ◽  
Vol 403 (3) ◽  
pp. 473-481 ◽  
Author(s):  
Ho-Jin Koh ◽  
Michael F. Hirshman ◽  
Huamei He ◽  
Yangfeng Li ◽  
Yasuko Manabe ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Activity ◽  
Chronic Exercise ◽  
Rat Adipocytes ◽  
Compound C ◽  
Isolated Adipocytes ◽  
Ampk Activity ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis.

scholarly journals Association of 5’AMP-activated protein kinase activity with disease duration and HbA1c content in leukocytes in diabetic patients

2019 ◽  
Vol 15 (1) ◽  
pp. 23-26
Author(s):  
L.K. Sokolova ◽  
V.M. Pushkarev ◽  
Yu.B. Belchina ◽  
V.V. Pushkarev ◽  
T.S. Vatseba ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Disease Duration ◽  
Diabetic Patients ◽  
Protein Kinase Activity ◽  
Amp Activated Protein Kinase

14-Deoxyandrographolide alleviates ethanol-induced hepatosteatosis through stimulation of AMP-activated protein kinase activity in rats

Alcohol ◽  
2014 ◽  
Vol 48 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Samir Mandal ◽  
Sibabrata Mukhopadhyay ◽  
Sukdeb Bandhopadhyay ◽  
Gargi Sen ◽  
Tuli Biswas
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Amp Activated Protein Kinase ◽  
Stimulation Of

scholarly journals Increased AMP:ATP Ratio and AMP-activated Protein Kinase Activity during Cellular Senescence Linked to Reduced HuR Function

2003 ◽  
Vol 278 (29) ◽  
pp. 27016-27023 ◽  
Author(s):  
Wengong Wang ◽  
Xiaoling Yang ◽  
Isabel López de Silanes ◽  
David Carling ◽  
Myriam Gorospe
Keyword(s):  
Protein Kinase ◽  
Cellular Senescence ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Amp Activated Protein Kinase

Measurement of AMP-Activated Protein Kinase Activity and Expression in Response to Ghrelin

2012 ◽  
pp. 271-287 ◽  
Author(s):  
Chung Thong Lim ◽  
Francesca Lolli ◽  
Julia D. Thomas ◽  
Blerina Kola ◽  
Márta Korbonits
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Amp Activated Protein Kinase

scholarly journals Regulation of 5′-AMP-activated Protein Kinase Activity by the Noncatalytic β and γ Subunits

1996 ◽  
Vol 271 (30) ◽  
pp. 17798-17803 ◽  
Author(s):  
Jason R. B. Dyck ◽  
Guang Gao ◽  
Jane Widmer ◽  
David Stapleton ◽  
C. Shamala Fernandez ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Amp Activated Protein Kinase
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