Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase

Journal article


Alesutan, Ioana, Munoz, Carlos, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Michael, Diana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Foller, Michael and Lang, Florian. (2011) Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 408(4), pp. 505 - 510. https://doi.org/10.1016/j.bbrc.2011.04.015
AuthorsAlesutan, Ioana, Munoz, Carlos, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Michael, Diana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Foller, Michael and Lang, Florian
Abstract

The inward rectifier K+ channel Kir2.1 participates in the maintenance of the cell membrane potential in a variety of cells including neurons and cardiac myocytes. Mutations of KCNJ2 encoding Kir2.1 underlie the Andersen–Tawil syndrome, a rare disorder clinically characterized by periodic paralysis, cardiac arrhythmia and skeletal abnormalities. The maintenance of the cardiac cell membrane potential is decreased in ischaemia, which is known to stimulate the AMP-activated serine/threonine protein kinase (AMPK). This energy-sensing kinase stimulates energy production and limits energy utilization. The present study explored whether AMPK regulates Kir2.1. To this end, cRNA encoding Kir2.1 was injected into Xenopus oocytes with and without additional injection of wild type AMPK (AMPKα1 + AMPKβ1 + AMPKγ1), of the constitutively active γR70QAMPK (α1β1γ1(R70Q)), of the kinase dead mutant αK45RAMPK (α1(K45R)β1γ1), or of the ubiquitin ligase Nedd4-2. Kir2.1 activity was determined in two-electrode voltage-clamp experiments. Moreover, Kir2.1 protein abundance in the cell membrane was determined by immunostaining and subsequent confocal imaging. As a result, wild type and constitutively active AMPK significantly reduced Kir2.1-mediated currents and Kir2.1 protein abundance in the cell membrane. Expression of wild type Nedd4-2 or of Nedd4-2S795A lacking an AMPK phosphorylation consensus sequence downregulated Kir2.1 currents. The effect of wild type Nedd4-2 but not of Nedd4-2S795Awas significantly augmented by additional coexpression of AMPK. In conclusion, AMPK is a potent regulator of Kir2.1. AMPK is at least partially effective through phosphorylation of the ubiquitin ligase Nedd4-2.

Year2011
JournalBiochemical and Biophysical Research Communications
Journal citation408 (4), pp. 505 - 510
ISSN0006-291X
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bbrc.2011.04.015
Page range505 - 510
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Fullerton, Morgan, Galic, Sandra, Marcinko, Katarina, Sikkema, Sarah, Pulinilkunnil, Thomas, Chen, Zhi-Ping, O'Neill, Hayley, Ford, Rebecca, Palanivel, Rengasamy, O'Brien, Matthew, Hardie, D. Grahame, Macaulay, Lance, Schertzer, Jonathan, Dyck, Jason, van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2013) Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nature Medicine. 19(12), pp. 1649 - 1654. https://doi.org/10.1038/nm.3372
AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice
O’Neill, Hayley M., Lally, James S., Galic, Sandra, Thomas, Melissa, Azizi, Paymon D., Fullerton, Morgan D., Smith, Brennan K., Pulinilkunnil, Thomas, Chen, Zhiping, Constantine Samaan, M., Jorgensen, Sebastian B., Dyck, Jason R. B., Holloway, Graham P., Hawke, Thomas J., van Denderen, Bryce J., Kemp, Bruce E. and Steinberg, Gregory R.. (2012) AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia. 57(8), pp. 1693 - 1702. https://doi.org/10.1007/s00125-014-3273-1
AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation
Zordoky, Beshay N.M., Nagendran, Jeevan, Pulinilkunnil, Thomas, Kienesberger, Petra C., Masson, Grant, Waller, Terri J., Kemp, Bruce E., Steinberg, Gregory R. and Dyck, Jason R. B.. (2012) AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation. Circulation Research. 115(5), pp. 518 - 524. https://doi.org/10.1161/CIRCRESAHA.115.304538
The ancient drug salicylate directly activates AMP-activated protein kinase
Hawley, Simon, Fullerton, Morgan, Ross, Fiona, Schertzer, Jonathan, Chevtzoff, Cyrille, Walker, Katherine, Peggie, Mark, Zibrova, Darya, Green, Kevin, Mustard, Kirsty, Kemp, Bruce, Sakamoto, Kei, Steinberg, Gregory and Hardie, D. Grahame. (2012) The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 336(6083), pp. 918 - 922. https://doi.org/10.1126/science.1215327
Pro-GRP-derived peptides are expressed in colorectal cancer cells and tumors and are biologically active in vivo
Patel, Oneel, Clyde, Daniel, Chang, Mike, Nordlund, Marianne, Steel, Rohan, Kemp, Bruce, Pritchard, D. Mark, Shulkes, Arthur and Baldwin, Graham. (2012) Pro-GRP-derived peptides are expressed in colorectal cancer cells and tumors and are biologically active in vivo. Endocrinology. 153(3), pp. 1082 - 1092. https://doi.org/10.1210/en.2011-1875
The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-ß1 deficient mice
Mount, Peter, Gleich, Kurt, Tam, Shanna, Fraser, Scott, Choy, Suet-Wan, Dwyer, Karen, Lu, Bo, Van Denderen, Bryce, Fingerle-Rowson, Gunter, Bucala, Richard, Kemp, Bruce and Power, David. (2012) The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-ß1 deficient mice. PLoS One (online). 7(1), pp. 1 - 10. https://doi.org/10.1371/journal.pone.0029887
Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase
Alesultan, Ioana, Foller, Michael, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Zelenak, Christine, Frohlich, Henning, Velic, Ana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Volkl, Harald and Lang, Florian. (2011) Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase. Molecular Membrane Biology. 28(2), pp. 79 - 89. https://doi.org/10.3109/09687688.2010.520037
AMP-activated protein kinase (AMPK) ß1ß2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise
O'Neill, Hayley M., Maarbjerg, Stine J., Crane, Justin D., Jeppesen, Jacob, Jorgensen, Sebastian B., Schertzer, Jonathan D., Shyroka, Olga, Kiens, Bente, Van Denderen, Bryce J., Tarnopolsky, Mark A., Kemp, Bruce Ernest, Richter, Erik A. and Steinberg, Gregory R.. (2011) AMP-activated protein kinase (AMPK) ß1ß2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proceedings of the National Academy of Sciences of USA. 108(38), pp. 16092 - 16097. https://doi.org/10.1073/pnas.1105062108
Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation
Green, Michelle, Scott, John, Steel, Rohan, Oakhill, Jonathan, Kemp, Bruce and Means, Anthony. (2011) Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation. Journal of Biological Chemistry. 286(32), pp. 28066 - 28079. https://doi.org/10.1074/jbc.M111.251504
Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Galic, Sandra, Fullerton, Morgan, Schertzer, Jonathan, Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl, Izon, David, Honeyman, Jane, Chen, Zhi-Ping, Van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2011) Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577
Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Galic, Sandra, Fullerton, Morgan D., Schertzer, Jonathan D., Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl R., Izon, David, Honeyman, Jane, Chen, Zhi-Ping, van Denderen, Bryce J., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2011) Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577
Inhibition of Connexin 26 by the AMP-activated protein kinase
Alesutan, Ioana, Sopjani, Mentor, Munoz, Carlos, Fraser, Scott, Kemp, Bruce, Foller, Michael and Lang, Florian. (2011) Inhibition of Connexin 26 by the AMP-activated protein kinase. Journal of Membrane Biology: an international journal for studies on the structure, function and genesis of biomembranes. 240(3), pp. 151 - 158. https://doi.org/10.1007/s00232-011-9353-y
AMPK is a direct adenylate charge-regulated protein kinase
Oakhill, Jonathan S., Steel, Rohan, Chen, Zhi-Ping, Scott, John W., Ling, Naomi, Tam, Shanna and Kemp, Bruce Ernest. (2011) AMPK is a direct adenylate charge-regulated protein kinase. Science. 332(6036), pp. 1433 - 1435. https://doi.org/10.1126/science.1200094
AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1
Fraser, Scott A., Choy, Suet-Wan, Pastor-Soler, Núria M., Li, Hui, Davies, Matthew R. P., Cook, Natasha, Katerelos, Marina, Mount, Peter F., Gleich, Kurt, McRae, Jennifer L., Dwyer, Karen M., van Denderen, Bryce J. W., Hallows, Kenneth R., Kemp, Bruce E. and Power, David A.. (2010) AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1. American Journal of Physiology - Renal Physiology. 305(5), pp. F679 - F690. https://doi.org/10.1152/ajprenal.00407.2012
Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity
Lessard, Sarah J., Rivas, Donato A., Chen, Zhu-Ping, van Denderen, Bryce J., Watt, Matthew J., Koch, Lauren G., Britton, Steven L., Kemp, Bruce Ernest and Hawley, John Alan. (2009) Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity. Endocrinology. 150(11), pp. 4883 - 4891. https://doi.org/10.1210/en.2009-0158
Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans
Yeo, Wee Kian, Lessard, Sarah J., Chen, Zhi-Ping, Garnham, Andrew P., Burke, Louise, Rivas, Donato A., Kemp, Bruce Ernest and Hawley, John Alan. (2008) Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans. Journal of Applied Physiology. 105(5), pp. 1519 - 1526. https://doi.org/10.1152/japplphysiol.90540.2008
Activation of AMPK reduces the co-transporter activity of NKCC1
Fraser, Scott A., Davies, Matthew, Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce E. and Power, David A.. (1999) Activation of AMPK reduces the co-transporter activity of NKCC1. Molecular Membrane Biology. 31(2-3), pp. 95 - 102. https://doi.org/10.3109/09687688.2014.902128
Myosin light chain kinases
Kemp, Bruce E. and Stull, James T.. (1990) Myosin light chain kinases. In In B. E. Kemp (Ed.). Peptides and Protein Phosphorylation pp. 115 - 133 CRC Press. https://doi.org/10.1201/9781351075442