AMP-activated protein kinase — the fat controller of the energy railroadThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

2006 ◽  
Vol 84 (7) ◽  
pp. 655-665 ◽  
Author(s):  
Gregory R. Steinberg ◽  
S. Lance Macaulay ◽  
Mark A Febbraio ◽  
Bruce E. Kemp
Keyword(s):  
Protein Kinase ◽  
Energy Demand ◽  
Second Messengers ◽  
Metabolic Stress ◽  
Special Issue ◽  
Endocrine Control ◽  
Fatty Acid Triglyceride ◽  
Amp Activated Protein Kinase ◽  
Major Mediator ◽  
Selection Of

AMP-activated protein kinase plays an important role in the regulation of lipid metabolism in response to metabolic stress and energy demand. It is also under endocrine control. AMPK acts at multiple steps and has a central role controlling fatty acid, triglyceride, and cholesterol synthesis, as well as the oxidation of fatty acids through direct phosphorylation effects and the control of gene transcription. As such, it can be considered to be the fat controller of the energy railroad. It is thought that AMPK may be a major mediator of the health benefits of exercise in mitigating the development of obesity and age-onset diseases.

AMP-activated protein kinase, super metabolic regulator

2003 ◽  
Vol 31 (1) ◽  
pp. 162-168 ◽  
Author(s):  
B.E. Kemp ◽  
D. Stapleton ◽  
D.J. Campbell ◽  
Z.-P. Chen ◽  
S. Murthy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Metabolic Pathways ◽  
Energy Demand ◽  
Metabolic Stress ◽  
Demand And Supply ◽  
Stress Sensing ◽  
Amp Activated Protein Kinase ◽  
Rate Limiting

The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to energy demand and supply by directly phosphorylating rate-limiting enzymes in metabolic pathways as well as controlling gene expression.

Dealing with energy demand: the AMP-activated protein kinase

1999 ◽  
Vol 24 (1) ◽  
pp. 22-25 ◽  
Author(s):  
Bruce E Kemp ◽  
Ken I Mitchelhill ◽  
David Stapleton ◽  
Belinda J Michell ◽  
Zhi-Ping Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Energy Demand ◽  
Amp Activated Protein Kinase

Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMP-activated protein kinase-related protein kinase, SNARK

2001 ◽  
Vol 355 (2) ◽  
pp. 297-305 ◽  
Author(s):  
Diana L. LEFEBVRE ◽  
Yahong BAI ◽  
Nazanin SHAHMOLKY ◽  
Monika SHARMA ◽  
Raymond POON ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cellular Response ◽  
Catalytic Domain ◽  
Metabolic Stress ◽  
Glucose Deprivation ◽  
Protein Band ◽  
Northern Blotting ◽  
Significant Similarity ◽  
Amp Activated Protein Kinase

Subtraction hybridization after the exposure of keratinocytes to ultraviolet radiation identified a differentially expressed cDNA that encodes a protein of 630 amino acid residues possessing significant similarity to the catalytic domain of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. Northern blotting and reverse-transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK-related kinase (SNARK) were widely expressed in rodent tissues. The SNARK gene was localized to human chromosome 1q32 by fluorescent in situ hybridization. SNARK was translated in vitro to yield a single protein band of approx. 76kDa; Western analysis of transfected baby hamster kidney (BHK) cells detected two SNARK-immunoreactive bands of approx. 76-80kDa. SNARK was capable of autophosphorylation in vitro; immunoprecipitated SNARK exhibited phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR (SAMS) as a kinase substrate. SNARK activity was significantly increased by AMP and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte cells, implying that SNARK might be activated by an AMPK kinase-dependent pathway. Furthermore, glucose deprivation increased SNARK activity 3-fold in BHK fibroblasts. These findings identify SNARK as a glucose- and AICAriboside-regulated member of the AMPK-related gene family that represents a new candidate mediator of the cellular response to metabolic stress.

Isoproterenol stimulates 5′-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts

2010 ◽  
Vol 299 (4) ◽  
pp. H1135-H1145 ◽  
Author(s):  
Jagdip S. Jaswal ◽  
Chad R. Lund ◽  
Wendy Keung ◽  
Donna L. Beker ◽  
Ivan M. Rebeyka ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Energy Demand ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Lactate Oxidation ◽  
Major Energy Source ◽  
Amp Activated Protein Kinase

Isoproterenol increases phosphorylation of LKB, 5′-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O2 consumption (in J·g dry wt−1·min−1; 11.0 ± 1.4, n = 8 vs. 7.5 ± 0.8, n = 6, P < 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 ± 0.09, n = 6 vs. 0.59 ± 0.08, n = 6, P < 0.05), AMPK (0.82 ± 0.08, n = 6 vs. 0.51 ± 0.06, n = 6, P < 0.05), and ACC-β (1.47 ± 0.14, n = 6 vs. 0.97 ± 0.07, n = 6, P < 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 ± 0.9, n = 8 vs. 7.5 ± 1.3, n = 8, P < 0.05) and increase in palmitate oxidation (in nmol·g dry wt−1·min−1; 272 ± 45, n = 8 vs. 114 ± 9, n = 6, P < 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt−1·min−1; 253 ± 75, n = 8 vs. 63 ± 15, n = 9, P < 0.05 and 246 ± 43, n = 8 vs. 82 ± 11, n = 6, P < 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation.

AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart

2015 ◽  
pp. 187-225
Author(s):  
Martin Pelosse ◽  
Malgorzata Tokarska-Schlattner ◽  
Uwe Schlattner
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Metabolic Stress ◽  
Stress Sensor ◽  
Amp Activated Protein Kinase ◽  
Kinase A

Muscle cell depolarization induces a gain in surface GLUT4 via reduced endocytosis independently of AMPK

2006 ◽  
Vol 290 (6) ◽  
pp. E1276-E1286 ◽  
Author(s):  
Nadeeja Wijesekara ◽  
Amanda Tung ◽  
Farah Thong ◽  
Amira Klip
Keyword(s):  
Protein Kinase ◽  
Energy Demand ◽  
Actin Polymerization ◽  
Membrane Depolarization ◽  
Akt Activation ◽  
L6 Myotubes ◽  
Dependent Protein ◽  
Cell Depolarization ◽  
Elevated Surface ◽  
Amp Activated Protein Kinase

Contracting skeletal muscle increases glucose uptake to sustain energy demand. This is achieved through a gain in GLUT4 at the membrane, but the traffic mechanisms and regulatory signals involved are unknown. Muscle contraction is elicited by membrane depolarization followed by a rise in cytosolic Ca2+ and actomyosin activation, drawing on ATP stores. It is unknown whether one or more of these events triggers the rise in surface GLUT4. Here, we investigate the effect of membrane depolarization on GLUT4 cycling using GLUT4 myc-expressing L6 myotubes devoid of sarcomeres and thus unable to contract. K+-induced membrane depolarization elevated surface GLUT4 myc, and this effect was additive to that of insulin, was not prevented by inhibiting phosphatidylinositol 3-kinase (PI3K) or actin polymerization, and did not involve Akt activation. Instead, depolarization elevated cytosolic Ca2+, and the surface GLUT4 myc elevation was prevented by dantrolene (an inhibitor of Ca2+ release from sarcoplasmic reticulum) and by extracellular Ca2+ chelation. Ca2+-calmodulin-dependent protein kinase-II (CaMKII) was not phosphorylated after 10 min of K+ depolarization, and the CaMK inhibitor KN62 did not prevent the gain in surface GLUT4 myc. Interestingly, although 5′-AMP-activated protein kinase (AMPK) was phosphorylated upon depolarization, lowering AMPKα via siRNA did not alter the surface GLUT4 myc gain. Conversely, the latter response was abolished by the PKC inhibitors bisindolylmaleimide I and calphostin C. Unlike insulin, K+ depolarization caused only a small increase in GLUT4 myc exocytosis and a major reduction in its endocytosis. We propose that K+ depolarization reduces GLUT4 internalization through signals and mechanisms distinct from those engaged by insulin. Such a pathway(s) is largely independent of PI3K, Akt, AMPK, and CaMKII but may involve PKC.

scholarly journals Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

2011 ◽  
Vol 31 (9) ◽  
pp. 3207-3216 ◽  
Author(s):  
C. I. Rodgers-Garlick ◽  
G. A. B. Armstrong ◽  
R. M. Robertson
Keyword(s):  
Protein Kinase ◽  
Metabolic Stress ◽  
Amp Activated Protein Kinase

5′-AMP-activated protein kinase is inactivated by adrenergic signalling in adult cardiac myocytes

2011 ◽  
Vol 32 (2) ◽  
pp. 197-209 ◽  
Author(s):  
Yugo Tsuchiya ◽  
Fiona C. Denison ◽  
Richard B. Heath ◽  
David Carling ◽  
David Saggerson
Keyword(s):  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Calcium Signalling ◽  
Metabolic Stress ◽  
Protein Kinase Activity ◽  
Adult Rat ◽  
Protein Kinase C Inhibitor ◽  
Amp Activated Protein Kinase

In adult rat cardiac myocytes adrenaline decreased AMPK (AMP-activated protein kinase) activity with a half-time of approximately 4 min, decreased phosphorylation of AMPK (α-Thr172) and decreased phosphorylation of ACC (acetyl-CoA carboxylase). Inactivation of AMPK by adrenaline was through both α1- and β-ARs (adrenergic receptors), but did not involve cAMP or calcium signalling, was not blocked by the PKC (protein kinase C) inhibitor BIM I (bisindoylmaleimide I), by the ERK (extracellular-signal-regulated kinase) cascade inhibitor U0126 or by PTX (pertussis toxin). Adrenaline caused no measurable change in LKB1 activity. Adrenaline decreased AMPK activity through a process that was distinct from AMPK inactivation in response to insulin or PMA. Neither adrenaline nor PMA altered the myocyte AMP:ATP ratio although the adrenaline effect was attenuated by oligomycin and by AICAR (5-amino-4-imidazolecarboxamide-1-β-D-ribofuranoside), agents that mimic ‘metabolic stress’. Inactivation of AMPK by adrenaline was abolished by 1 μM okadaic acid suggesting that activation of PP2A (phosphoprotein phosphatase 2A) might mediate the adrenaline effect. However, no change in PP2A activity was detected in myocyte extracts. Adrenaline increased phosphorylation of the AMPK β-subunit in vitro but there was no detectable change in vivo in phosphorylation of previously identified AMPK sites (β-Ser24, β-Ser108 or β-Ser182) suggesting that another site(s) is targeted.

AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer

2011 ◽  
Vol 39 (1) ◽  
pp. 1-13 ◽  
Author(s):  
D. Grahame Hardie
Keyword(s):  
Protein Kinase ◽  
Metabolic Disorders ◽  
Adenine Nucleotides ◽  
Metabolic Stress ◽  
Branch Points ◽  
Atp Production ◽  
Nucleotide Binding Sites ◽  
Anticancer Effects ◽  
Energy Sensor ◽  
Amp Activated Protein Kinase

It is essential to life that a balance is maintained between processes that produce ATP and those that consume it. An obvious way to do this would be to have systems that monitor the levels of ATP and ADP, although because of the adenylate kinase reaction (2ADP↔ATP+AMP), AMP is actually a more sensitive indicator of energy stress than ADP. Following the discoveries that glycogen phosphorylase and phosphofructokinase were regulated by AMP and ATP, Daniel Atkinson proposed that all enzymes at branch points between biosynthesis and degradation would be regulated by adenine nucleotides. This turned out to be correct, but what Atkinson did not anticipate was that sensing of nucleotides would, in most cases, be performed not by the metabolic enzymes themselves, but by a signalling protein, AMPK (AMP-activated protein kinase). AMPK occurs in essentially all eukaryotes and consists of heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits, of which the latter carries the nucleotide-binding sites. Once activated by a metabolic stress, it phosphorylates numerous targets that alter enzyme activity and gene expression to initiate corrective responses. In lower eukaryotes, it is critically involved in the responses to starvation for a carbon source. Because of its ability to switch cellular metabolism from anabolic to catabolic mode, AMPK has become a key drug target to combat metabolic disorders associated with overnutrition such as Type 2 diabetes, and some existing anti-diabetic drugs (e.g. metformin) and many ‘nutraceuticals’ work by activating AMPK, usually via inhibition of mitochondrial ATP production. AMPK activators also potentially have anticancer effects, and there is already evidence that metformin provides protection against the initiation of cancer. Whether AMPK activators can be used to treat existing cancer is less clear, because many tumour cells appear to have been selected for mutations that inactivate the AMPK system. However, if we can identify the various mechanisms by which this occurs, we may be able to find ways of overcoming it.

Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles

2002 ◽  
Vol 283 (1) ◽  
pp. E178-E186 ◽  
Author(s):  
Paula E. Durante ◽  
Kirsty J. Mustard ◽  
Soo-Hyun Park ◽  
William W. Winder ◽  
D. Grahame Hardie
Keyword(s):  
Protein Kinase ◽  
Endurance Training ◽  
Treadmill Exercise ◽  
Metabolic Stress ◽  
Special Role ◽  
Acetyl Coa Carboxylase ◽  
Threefold Increase ◽  
Subunit Isoforms ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise

The effects of endurance training on the response of muscle AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) to moderate treadmill exercise were examined. In red quadriceps, there was a large activation of α2-AMPK and inactivation of ACC in response to exercise. This response was greatly reduced after training, probably because of reduced metabolic stress. In white quadriceps, there were no effects of exercise on AMPK or ACC, but α2-activity was higher after training because of increased phosphorylation of Thr172. In soleus, there were small increases in α2-activity during exercise that were not affected by training. The expression of all seven AMPK subunit isoforms was also examined. The β2- and γ2-isoforms were most highly expressed in white quadriceps, and γ3 was expressed in red quadriceps and soleus. There was a threefold increase in expression of γ3 after training in red quadriceps only. Our results suggest that γ3 might have a special role in the adaptation to endurance exercise in muscles utilizing oxidative metabolism.

Sign in / Sign up

Export Citation Format

Share Document