AMP-activated protein kinase: Nature's energy sensor

被引：0
作者：
Carling D. [1 ]
Mayer F.V. [1 ]
Sanders M.J. [2 ]
Gamblin S.J. [2 ]
机构：
[1] Medical Research Council (MRC) Clinical Sciences Centre, Hammersmith Hospital Campus, Imperial College, London
[2] MRC National Institute for Medical Research, London
来源：
Nature Chemical Biology | 2011年 / 7卷 / 8期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1038/nchembio.610
中图分类号：
学科分类号：
摘要：
Maintaining sufficient levels of ATP (the immediate source of cellular energy) is essential for the proper functioning of all living cells. As a consequence, cells require mechanisms to balance energy demand with supply. In eukaryotic cells the AMP-activated protein kinase (AMPK) cascade has an important role in this homeostasis. AMPK is activated by a fall in ATP (concomitant with a rise in ADP and AMP), which leads to the activation of catabolic pathways and the inhibition of anabolic pathways. Here we review the role of AMPK as an energy sensor and consider the recent finding that ADP, as well as AMP, causes activation of mammalian AMPK. We also review recent progress in structural studies on phosphorylated AMPK that provides a mechanism for the regulation of AMPK in which AMP and ADP protect it against dephosphorylation. Finally, we briefly survey some of the outstanding questions concerning the regulation of AMPK. © 2011 Nature America, Inc. All rights reserved.
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页码：512 / 518
页数：6
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共 80 条
  • [1] Boyer P.D., Et al., Oxidative phosphorylation and photophosphorylation, Annu. Rev. Biochem., 46, pp. 955-966, (1977)
  • [2] Carling D., Zammit V.A., Hardie D.G., A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis, FEBS Lett., 223, pp. 217-222, (1987)
  • [3] Hardie D.G., Carling D., Sim A.T.R., The AMP-activated protein kinase: A multisubstrate regulator of lipid metabolism, Trends in Biochemical Sciences, 14, 1, pp. 20-23, (1989)
  • [4] Carlson C.A., Kim K.H., Regulation of hepatic acetyl-CoA carboxylase by phosphorylation and dephosphorylation, J. Biol. Chem., 248, pp. 378-380, (1973)
  • [5] Yeh L.A., Lee K.H., Kim K.H., Regulation of rat liver acetyl-CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl-CoA carboxylase by the adenylate energy charge, Journal of Biological Chemistry, 255, 6, pp. 2308-2314, (1980)
  • [6] Beg Z.H., Allmann D.W., Gibson D.M., Modulation of 3-hydroxy-3- methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol, Biochem. Biophys. Res. Commun., 54, pp. 1362-1369, (1973)
  • [7] Harwood Jr. H.J., Brandt K.G., Rodwell V.W., Allosteric activation of rat liver cytosylic 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase by nucleoside diphosphates, Journal of Biological Chemistry, 259, 5, pp. 2810-2815, (1984)
  • [8] Ingebritsen T.S., Parker R.A., Gibson D.M., Regulation of liver hydroxymethylglutaryl-CoA reductase by a bicyclic phosphorylation system, Journal of Biological Chemistry, 256, 3, pp. 1138-1144, (1981)
  • [9] Hardie D.G., Carling D., Carlson M., The AMP-activated/SNF1 protein kinase subfamily: Metabolic sensors of the eukaryotic cell?, Annual Review of Biochemistry, 67, pp. 821-855, (1998)
  • [10] Munday M.R., Campbell D.G., Carling D., Hardie D.G., Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase, Eur. J. Biochem., 175, pp. 331-338, (1988)
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