Prkaa2

Summary

Gene Symbol: Prkaa2
Description: protein kinase, AMP-activated, alpha 2 catalytic subunit
Alias: 2310008I11Rik, A830082D05, AMPKalpha2, 5'-AMP-activated protein kinase catalytic subunit alpha-2, ACACA kinase, AMP-activated protein kinase alpha-2 variant B, AMPK subunit alpha-2, HMGCR kinase, acetyl-CoA carboxylase kinase, hydroxymethylglutaryl-CoA reductase kinase
Species: mouse
Products:     Prkaa2

Top Publications

  1. Villena J, Viollet B, Andreelli F, Kahn A, Vaulont S, Sul H. Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit. Diabetes. 2004;53:2242-9 pubmed
    ..In the present study, we subjected AMPKalpha2 knockout (KO) mice to a high-fat diet to examine the effect of AMPK on adipose tissue formation...
  2. Laderoute K, Amin K, Calaoagan J, Knapp M, Le T, Orduna J, et al. 5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol. 2006;26:5336-47 pubmed
    ..We also showed that AMPK is important for the growth of this tumor model. ..
  3. Suzuki A, Okamoto S, Lee S, Saito K, Shiuchi T, Minokoshi Y. Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase. Mol Cell Biol. 2007;27:4317-27 pubmed
    ..Our data thus suggest that the activation of and changes in the subcellular localization of alpha2AMPK are required for leptin-induced stimulation of fatty acid oxidation and PPARalpha gene expression in muscle cells. ..
  4. Scharf M, Mackiewicz M, Naidoo N, O Callaghan J, Pack A. AMP-activated protein kinase phosphorylation in brain is dependent on method of killing and tissue preparation. J Neurochem. 2008;105:833-41 pubmed
    ..These results demonstrate that alpha-AMPK phosphorylation is dependent on method of killing and tissue preparation and that alpha-AMPK phosphorylation can increase in a manner that does not reflect biological alterations. ..
  5. Xie Z, Zhang J, Wu J, Viollet B, Zou M. Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes. Diabetes. 2008;57:3222-30 pubmed publisher
    ..and prostacyclin synthase nitration in diabetic wild-type mice but not in their AMPKalpha2-deficient counterparts in vivo...
  6. Claret M, Smith M, Batterham R, Selman C, Choudhury A, Fryer L, et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest. 2007;117:2325-36 pubmed
  7. Viollet B, Andreelli F, Jørgensen S, Perrin C, Flamez D, Mu J, et al. Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. Biochem Soc Trans. 2003;31:216-9 pubmed
    ..We suggest that the alpha2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo. ..
  8. Röckl K, Hirshman M, Brandauer J, Fujii N, Witters L, Goodyear L. Skeletal muscle adaptation to exercise training: AMP-activated protein kinase mediates muscle fiber type shift. Diabetes. 2007;56:2062-9 pubmed
    ..this training-induced shift was reduced by approximately 40% in transgenic mice expressing a muscle-specific AMPKalpha2 inactive subunit. Sedentary mice carrying an AMPK-activating mutation (gamma1TG) showed a 2...
  9. Martin T, Alquier T, Asakura K, Furukawa N, Preitner F, Kahn B. Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle. J Biol Chem. 2006;281:18933-41 pubmed
    ..Defective responses of AMPK to leptin may contribute to resistance to leptin action on food intake and energy expenditure in obese states. ..

More Information

Publications78

  1. Liu C, Liang B, Wang Q, Wu J, Zou M. Activation of AMP-activated protein kinase alpha1 alleviates endothelial cell apoptosis by increasing the expression of anti-apoptotic proteins Bcl-2 and survivin. J Biol Chem. 2010;285:15346-55 pubmed publisher
    ..Finally, we found that genetic deletion of the AMPKalpha1, but not AMPKalpha2, suppressed OGD-enhanced NF-kappaB activation, the expression of Bcl-2 and Survivin, and endothelial apoptosis...
  2. Shinmura K, Tamaki K, Saito K, Nakano Y, Tobe T, Bolli R. Cardioprotective effects of short-term caloric restriction are mediated by adiponectin via activation of AMP-activated protein kinase. Circulation. 2007;116:2809-17 pubmed
    ..The cardioprotective effects of short-term CR are mediated by increased production of adiponectin and the associated activation of AMP-activated protein kinase. ..
  3. Davis B, Xie Z, Viollet B, Zou M. Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes. 2006;55:496-505 pubmed
    ..Taken together, our results indicate that metformin might improve vascular endothelial functions in diabetes by increasing AMPK-dependent, hsp90-mediated eNOS activation. ..
  4. Hezel A, Gurumurthy S, Granot Z, Swisa A, Chu G, Bailey G, et al. Pancreatic LKB1 deletion leads to acinar polarity defects and cystic neoplasms. Mol Cell Biol. 2008;28:2414-25 pubmed publisher
    ..These genetic studies provide in vivo evidence of a key role for LKB1 in the establishment of epithelial cell polarity that is vital for pancreatic acinar cell function and viability and for the suppression of neoplasia. ..
  5. Pehmøller C, Treebak J, Birk J, Chen S, MacKintosh C, Hardie D, et al. Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2009;297:E665-75 pubmed publisher
    ..Thus, TBC1D1 is differentially regulated in response to insulin and contraction. This study provides genetic evidence to support an important role for AMPK in regulating TBC1D1 in response to both of these physiological stimuli. ..
  6. Treebak J, Glund S, Deshmukh A, Klein D, Long Y, Jensen T, et al. AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes. 2006;55:2051-8 pubmed
    ..Contraction-mediated AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK. ..
  7. Foretz M, Hebrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest. 2010;120:2355-69 pubmed publisher
    ..In conclusion, we demonstrate that metformin inhibits hepatic gluconeogenesis in an LKB1- and AMPK-independent manner via a decrease in hepatic energy state. ..
  8. Jørgensen S, Treebak J, Viollet B, Schjerling P, Vaulont S, Wojtaszewski J, et al. Role of AMPKalpha2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle. Am J Physiol Endocrinol Metab. 2007;292:E331-9 pubmed
    ..In both muscle types, AMPKalpha2 activity was increased in response to both stimuli, whereas AMPKalpha1 activity was increased only in response ..
  9. Viollet B, Andreelli F, Jørgensen S, Perrin C, Geloen A, Flamez D, et al. The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest. 2003;111:91-8 pubmed
    ..To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated...
  10. Zhang J, Xie Z, Dong Y, Wang S, Liu C, Zou M. Identification of nitric oxide as an endogenous activator of the AMP-activated protein kinase in vascular endothelial cells. J Biol Chem. 2008;283:27452-61 pubmed publisher
    ..Taken together, we conclude that NO might act as an endogenous AMPK activator. ..
  11. Beall C, Piipari K, Al Qassab H, Smith M, Parker N, Carling D, et al. Loss of AMP-activated protein kinase alpha2 subunit in mouse beta-cells impairs glucose-stimulated insulin secretion and inhibits their sensitivity to hypoglycaemia. Biochem J. 2010;429:323-33 pubmed publisher
    ..These results show that AMPK alpha2 activity is necessary to maintain normal pancreatic beta-cell glucose sensing, possibly by maintaining high beta-cell levels of UCP2. ..
  12. Jeppesen J, Albers P, Rose A, Birk J, Schjerling P, Dzamko N, et al. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent. J Lipid Res. 2011;52:699-711 pubmed publisher
    ..However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations. ..
  13. Wang S, Zhang M, Liang B, Xu J, Xie Z, Liu C, et al. AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes. Circ Res. 2010;106:1117-28 pubmed publisher
    ..p50 and p65) were examined in cultured human umbilical vein endothelial cells and mouse aortas isolated from AMPKalpha2 deficient mice...
  14. Peck G, Chavez J, Roach W, Budnik B, Lane W, Karlsson H, et al. Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1 regulates GLUT4 translocation. J Biol Chem. 2009;284:30016-23 pubmed publisher
    ..In conclusion, phosphorylation of TBC1D1 is required for GLUT4 translocation. Thus, the regulation of TBC1D1 resembles that of its paralog, AS160. ..
  15. Gwinn D, Shackelford D, Egan D, Mihaylova M, Mery A, Vasquez D, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008;30:214-26 pubmed publisher
    ..These findings uncover a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status. ..
  16. Frøsig C, Pehmøller C, Birk J, Richter E, Wojtaszewski J. Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle. J Physiol. 2010;588:4539-48 pubmed publisher
    ..Furthermore, we show that the catalytic ?2 AMPK subunit is the main (but probably not the only) donor of AMPK activity regulating TBC1D1 Ser237 phosphorylation in mouse EDL muscle. ..
  17. Zwetsloot K, Westerkamp L, Holmes B, Gavin T. AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise. J Physiol. 2008;586:6021-35 pubmed publisher
  18. Zhang P, Hu X, Xu X, Fassett J, Zhu G, Viollet B, et al. AMP activated protein kinase-alpha2 deficiency exacerbates pressure-overload-induced left ventricular hypertrophy and dysfunction in mice. Hypertension. 2008;52:918-24 pubmed publisher
    ..To test the hypothesis that AMPKalpha2 protects the heart against systolic overload-induced ventricular hypertrophy and dysfunction, we studied the ..
  19. Um J, Yang S, Yamazaki S, Kang H, Viollet B, Foretz M, et al. Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. J Biol Chem. 2007;282:20794-8 pubmed
    ..We conclude that metformin and AMPK have a previously unrecognized role in regulating the circadian rhythm. ..
  20. Maarbjerg S, Jørgensen S, Rose A, Jeppesen J, Jensen T, Treebak J, et al. Genetic impairment of AMPKalpha2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Am J Physiol Endocrinol Metab. 2009;297:E924-34 pubmed publisher
    ..We studied this in male and female mice overexpressing kinase-dead AMPKalpha2 (AMPK-KD) in skeletal and heart muscles...
  21. Kim J, Kundu M, Viollet B, Guan K. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13:132-41 pubmed publisher
    ..This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling. ..
  22. Zong H, Ren J, Young L, Pypaert M, Mu J, Birnbaum M, et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A. 2002;99:15983-7 pubmed
    ..These data demonstrate that by sensing the energy status of the muscle cell, AMPK is a critical regulator involved in initiating mitochondrial biogenesis. ..
  23. Fujii N, Hirshman M, Kane E, Ho R, Peter L, Seifert M, et al. AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle. J Biol Chem. 2005;280:39033-41 pubmed
    ..Muscle contraction- and hyperosmolarity-induced glucose transport may be regulated by a redundant mechanism in which AMPK alpha2 is one of multiple signaling pathways. ..
  24. Dzamko N, Schertzer J, Ryall J, Steel R, Macaulay S, Wee S, et al. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J Physiol. 2008;586:5819-31 pubmed publisher
    ..These data demonstrate that AMPK is not essential for the regulation of fatty acid oxidation by AICAR or muscle contraction. ..
  25. Kovacic S, Soltys C, Barr A, Shiojima I, Walsh K, Dyck J. Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem. 2003;278:39422-7 pubmed
    ..In addition, our data suggest that the ability of insulin to inhibit AMPK may be controlled via an Akt-mediated mechanism. ..
  26. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes. 2005;54:1331-9 pubmed
    ..specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA)...
  27. Lamia K, Sachdeva U, DiTacchio L, Williams E, Alvarez J, Egan D, et al. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science. 2009;326:437-40 pubmed publisher
    ..Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs. ..
  28. Guigas B, Taleux N, Foretz M, Detaille D, Andreelli F, Viollet B, et al. AMP-activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside. Biochem J. 2007;404:499-507 pubmed
    ..Our data also demonstrate that the cellular effects of AICA riboside are not necessarily caused by AMPK activation and that their interpretation should be taken with caution. ..
  29. Guigas B, Bertrand L, Taleux N, Foretz M, Wiernsperger N, Vertommen D, et al. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. Diabetes. 2006;55:865-74 pubmed
  30. Göransson O, McBride A, Hawley S, Ross F, Shpiro N, Foretz M, et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem. 2007;282:32549-60 pubmed
    ..We propose that this direct and specific AMPK activator will be a valuable experimental tool to understand the physiological roles of AMPK. ..
  31. Andreelli F, Foretz M, Knauf C, Cani P, Perrin C, Iglesias M, et al. Liver adenosine monophosphate-activated kinase-alpha2 catalytic subunit is a key target for the control of hepatic glucose production by adiponectin and leptin but not insulin. Endocrinology. 2006;147:2432-41 pubmed
    ..Here we studied how hepatic AMPKalpha2 isoform affects hepatic glucose production and peripheral glucose uptake in vivo...
  32. Fujii N, Ho R, Manabe Y, Jessen N, Toyoda T, Holland W, et al. Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice. Diabetes. 2008;57:2958-66 pubmed publisher
    ..g., metformin) treatments. ..
  33. Shaw R, Lamia K, Vasquez D, Koo S, Bardeesy N, Depinho R, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310:1642-6 pubmed
    ..Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels. ..
  34. Fu X, Zhao J, Zhu M, Foretz M, Viollet B, Dodson M, et al. AMP-activated protein kinase ?1 but not ?2 catalytic subunit potentiates myogenin expression and myogenesis. Mol Cell Biol. 2013;33:4517-25 pubmed publisher
    ..In summary, these results indicate that AMPK activity promotes myogenesis through a mechanism mediated by AMPK?1. ..
  35. Sun G, Tarasov A, McGinty J, McDonald A, da Silva Xavier G, Gorman T, et al. Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo. Diabetologia. 2010;53:924-36 pubmed publisher
    ..beta cells and hypothalamic neurons by breeding Ampkalpha1 [also known as Prkaa1]-knockout mice, bearing floxed Ampkalpha2 [also known as Prkaa2] alleles (Ampkalpha1 ( -/- ),alpha2( fl/fl ),), with mice expressing Cre recombinase under ..
  36. Jørgensen S, Viollet B, Andreelli F, Frøsig C, Birk J, Schjerling P, et al. Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. J Biol Chem. 2004;279:1070-9 pubmed
    ..Alternatively, neither alpha-isoform of AMPK is involved in contraction-induced muscle glucose uptake. ..
  37. Howell J, Hellberg K, Turner M, Talbott G, Kolar M, Ross D, et al. Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex. Cell Metab. 2017;25:463-471 pubmed publisher
    ..Finally, we show that metformin profoundly inhibits hepatocyte protein synthesis in a manner that is largely dependent on its ability to suppress mTORC1 signaling. ..
  38. Bultot L, Guigas B, von Wilamowitz Moellendorff A, Maisin L, Vertommen D, Hussain N, et al. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase. Biochem J. 2012;443:193-203 pubmed publisher
    ..The results suggest that GYS inactivation by AMPK activators in hepatocytes is due to GYS2 Ser7 phosphorylation. ..
  39. Song P, Zhou Y, Coughlan K, Dai X, Xu H, Viollet B, et al. Adenosine monophosphate-activated protein kinase-?2 deficiency promotes vascular smooth muscle cell migration via S-phase kinase-associated protein 2 upregulation and E-cadherin downregulation. Arterioscler Thromb Vasc Biol. 2013;33:2800-9 pubmed publisher
    ..Finally, neointima formation after ligation of carotid artery was increased in AMPK?2(-/-), but not AMPK?1(-/-), mice. We conclude that deletion of AMPK?2 causes aberrant VSMC migration with accelerated neointima formation in vivo. ..
  40. Oudit G, Liu G, Zhong J, Basu R, Chow F, Zhou J, et al. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes. 2010;59:529-38 pubmed publisher
    ..In vitro studies show that the protective effect of hrACE2 is due to reduction in ANG II and an increase in ANG 1-7 signaling. ..
  41. Lieberthal W, Zhang L, Patel V, Levine J. AMPK protects proximal tubular cells from stress-induced apoptosis by an ATP-independent mechanism: potential role of Akt activation. Am J Physiol Renal Physiol. 2011;301:F1177-92 pubmed publisher
    ..Protection by AMPK appears to be due not to AMPK-mediated conservation of cell energy stores, but rather, at least in part, to AMPK-mediated activation of Akt. ..
  42. Gongol B, Marin T, Peng I, Woo B, Martin M, King S, et al. AMPK?2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6. Proc Natl Acad Sci U S A. 2013;110:3161-6 pubmed publisher
    ..Conversely, AMPK? suppression or knockdown produces the opposite effects. The results demonstrate an anti-infamatory pathway linking AMPK, PARP-1, and Bcl-6 in endothelial cells. ..
  43. Li Y, Xu S, Mihaylova M, Zheng B, Hou X, Jiang B, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13:376-388 pubmed publisher
    ..AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis. ..
  44. Kelly M, Gauthier M, Saha A, Ruderman N. Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization. Diabetes. 2009;58:1953-60 pubmed publisher
  45. Bess E, Fisslthaler B, Frömel T, Fleming I. Nitric oxide-induced activation of the AMP-activated protein kinase ?2 subunit attenuates I?B kinase activity and inflammatory responses in endothelial cells. PLoS ONE. 2011;6:e20848 pubmed publisher
    ..Moreover, as NO potently activates AMPK in endothelial cells, a portion of the anti-inflammatory effects of NO are mediated by AMPK. ..
  46. Chen Q, Xie B, Zhu S, Rong P, Sheng Y, Ducommun S, et al. A Tbc1d1 Ser231Ala-knockin mutation partially impairs AICAR- but not exercise-induced muscle glucose uptake in mice. Diabetologia. 2017;60:336-345 pubmed publisher
    ..TBC1D1-Ser231 phosphorylation and/or 14-3-3 binding partially mediates AMPK-governed glucose homeostasis and muscle glucose uptake in a context-dependent manner. ..
  47. Lai Y, Kviklyte S, Vertommen D, Lantier L, Foretz M, Viollet B, et al. A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators. Biochem J. 2014;460:363-75 pubmed publisher
    ..In summary, ex229 efficiently activated skeletal muscle AMPK and elicited metabolic effects in muscle appropriate for treating Type 2 diabetes by stimulating glucose uptake and increasing fatty acid oxidation. ..
  48. Slámová K, Papoušek F, Janovská P, Kopecký J, Kolář F. Adverse effects of AMP-activated protein kinase alpha2-subunit deletion and high-fat diet on heart function and ischemic tolerance in aged female mice. Physiol Res. 2016;65:33-42 pubmed
    ..The results demonstrate that adverse effects of AMPK alpha2-subunit deletion and high-fat feeding on heart function and myocardial ischemic tolerance in aged female mice are not additive. ..
  49. Stahmann N, Woods A, Spengler K, Heslegrave A, Bauer R, Krause S, et al. Activation of AMP-activated protein kinase by vascular endothelial growth factor mediates endothelial angiogenesis independently of nitric-oxide synthase. J Biol Chem. 2010;285:10638-52 pubmed publisher
    ..To investigate the role of AMPK in endothelial function, CaMKKbeta, AMPKalpha1, or AMPKalpha2 was down-regulated by RNA interference, and studies in AMPKalpha1(-/-) mice were performed...
  50. Ollila S, Domènech Moreno E, Laajanen K, Wong I, Tripathi S, Pentinmikko N, et al. Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL-11-JAK/STAT3 pathway. J Clin Invest. 2018;128:402-414 pubmed publisher
    ..These data indicate that IL-11-mediated induction of JAK/STAT3 is critical in gastrointestinal tumorigenesis following Lkb1 mutations and suggest that targeting this pathway has therapeutic potential in Peutz-Jeghers syndrome. ..
  51. Athea Y, Viollet B, Mateo P, Rousseau D, Novotova M, Garnier A, et al. AMP-activated protein kinase alpha2 deficiency affects cardiac cardiolipin homeostasis and mitochondrial function. Diabetes. 2007;56:786-94 pubmed
    ..Here, we investigated whether deletion of AMPKalpha2, the main cardiac catalytic isoform, alters mitochondrial function and biogenesis...
  52. Egawa T, Goto A, Ohno Y, Yokoyama S, Ikuta A, Suzuki M, et al. Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice. Am J Physiol Endocrinol Metab. 2015;309:E651-62 pubmed publisher
    ..These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system. ..
  53. Schulz E, Anter E, Zou M, Keaney J. Estradiol-mediated endothelial nitric oxide synthase association with heat shock protein 90 requires adenosine monophosphate-dependent protein kinase. Circulation. 2005;111:3473-80 pubmed
    ..These data point to a novel role for AMPK in modulating endothelial cell NO bioactivity and HSP90 function. ..
  54. Fentz J, Kjøbsted R, Kristensen C, Hingst J, Birk J, Gudiksen A, et al. AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2015;309:E900-14 pubmed publisher
  55. Li G, Wang J, Ye J, Zhang Y, Zhang Y. PPARα Protein Expression Was Increased by Four Weeks of Intermittent Hypoxic Training via AMPKα2-Dependent Manner in Mouse Skeletal Muscle. PLoS ONE. 2015;10:e0122593 pubmed publisher
    ..Our data suggest that the increase in nuclear PPARα protein by four-week exercise training under the intermittent hypoxia was dependent on AMPK activation. ..
  56. Carvajal K, Zarrinpashneh E, Szarszoi O, Joubert F, Athea Y, Mateo P, et al. Dual cardiac contractile effects of the alpha2-AMPK deletion in low-flow ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 2007;292:H3136-47 pubmed
    ..In conclusion, alpha(2)-AMPK is required for a normal glucose uptake and glycogen content, which protects the heart from the development of the ischemic contracture, but not for contractile recovery in the absence of fatty acids. ..
  57. Glund S, Treebak J, Long Y, Barres R, Viollet B, Wojtaszewski J, et al. Role of adenosine 5'-monophosphate-activated protein kinase in interleukin-6 release from isolated mouse skeletal muscle. Endocrinology. 2009;150:600-6 pubmed publisher
    ..Skeletal muscle from AMPKalpha2 kinase-dead transgenic, AMPKalpha1 knockout (KO) and AMPKgamma3 KO mice and respective wild-type littermates was ..
  58. Schisler J, Rubel C, Zhang C, Lockyer P, Cyr D, Patterson C. CHIP protects against cardiac pressure overload through regulation of AMPK. J Clin Invest. 2013;123:3588-99 pubmed publisher
  59. Peterson S, Kim D, Li M, Positano V, Vanella L, Rodella L, et al. The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice. J Lipid Res. 2009;50:1293-304 pubmed publisher
    ..The anti-obesity effects of L-4F are manifested by a decrease in visceral fat content with reciprocal increases in adiponectin, pAMPK, pAKT, and phosphorylation of insulin receptors with improved insulin sensitivity. ..
  60. Qiu S, Xiao Z, Piao C, Xian Y, Jia L, Qi Y, et al. AMP-activated protein kinase ?2 protects against liver injury from metastasized tumors via reduced glucose deprivation-induced oxidative stress. J Biol Chem. 2014;289:9449-59 pubmed publisher
    ..Therefore, AMPK ?2 might represent an important therapeutic target for colon cancer metastasis-induced liver injury. ..
  61. Balteau M, Van Steenbergen A, Timmermans A, Dessy C, Behets Wydemans G, Tajeddine N, et al. AMPK activation by glucagon-like peptide-1 prevents NADPH oxidase activation induced by hyperglycemia in adult cardiomyocytes. Am J Physiol Heart Circ Physiol. 2014;307:H1120-33 pubmed publisher
    ..In conclusion, GLP-1 induces ?2-AMPK activation and blocks HG-induced p47phox translocation to the plasma membrane, thereby preventing glucotoxicity. ..
  62. Sylow L, Møller L, Kleinert M, D Hulst G, De Groote E, Schjerling P, et al. Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise. Diabetes. 2017;66:1548-1559 pubmed publisher
    ..It is concluded that Rac1 and AMPK together account for almost the entire ex vivo contraction response in muscle glucose transport, whereas only Rac1, but not ?2 AMPK, regulates muscle glucose uptake during submaximal exercise in vivo. ..
  63. Djouder N, Tuerk R, Suter M, Salvioni P, Thali R, Scholz R, et al. PKA phosphorylates and inactivates AMPKalpha to promote efficient lipolysis. EMBO J. 2010;29:469-81 pubmed publisher
    ..These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response. ..
  64. Wan L, Xu K, Wei Y, Zhang J, Han T, Fry C, et al. Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function. Mol Cell. 2018;69:279-291.e5 pubmed publisher
    ..Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies. ..
  65. Chan A, Dolinsky V, Soltys C, Viollet B, Baksh S, Light P, et al. Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt. J Biol Chem. 2008;283:24194-201 pubmed publisher
    ..Taken together, our data suggest that resveratrol exerts anti-hypertrophic effects by activating AMPK via LKB1 and inhibiting Akt, thus suppressing protein synthesis and gene transcription...
  66. Chang M, Ho F, Wang J, Kang H, Chang Y, Ye Z, et al. AICAR induces cyclooxygenase-2 expression through AMP-activated protein kinase-transforming growth factor-beta-activated kinase 1-p38 mitogen-activated protein kinase signaling pathway. Biochem Pharmacol. 2010;80:1210-20 pubmed publisher
    ..Furthermore, we also found that TAK1 is associated with AMPKalpha2, and this binding requires an interaction between the kinase domains of both molecules...
  67. Xing J, Wang Q, Coughlan K, Viollet B, Moriasi C, Zou M. Inhibition of AMP-activated protein kinase accentuates lipopolysaccharide-induced lung endothelial barrier dysfunction and lung injury in vivo. Am J Pathol. 2013;182:1021-30 pubmed publisher
    ..We conclude that AMPK activity supports normal endothelial barrier function and that LPS exposure inhibits AMPK, thereby contributing to endothelial barrier dysfunction and lung injury. ..
  68. Emerling B, Weinberg F, Snyder C, Burgess Z, Mutlu G, Viollet B, et al. Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radic Biol Med. 2009;46:1386-91 pubmed publisher
    ..Collectively, these data indicate that oxidative stress and not an increase in the AMP/ATP ratio is required for hypoxic activation of AMPK. ..
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