D G Hardie

Summary

Affiliation: University of Dundee
Country: UK

Publications

  1. doi request reprint A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
    Mhairi C Towler
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Biochem J 416:1-14. 2008
  2. ncbi request reprint AMP-Activated Protein Kinase: Maintaining Energy Homeostasis at the Cellular and Whole-Body Levels
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, United Kingdom email
    Annu Rev Nutr 34:31-55. 2014
  3. pmc C-terminal phosphorylation of LKB1 is not required for regulation of AMP-activated protein kinase, BRSK1, BRSK2, or cell cycle arrest
    Sarah Fogarty
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 284:77-84. 2009
  4. pmc Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP
    Sarah Fogarty
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U K
    Biochem J 426:109-18. 2010
  5. pmc AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation
    Graeme J Gowans
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Cell Metab 18:556-66. 2013
  6. pmc AMPK: a target for drugs and natural products with effects on both diabetes and cancer
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Diabetes 62:2164-72. 2013
  7. pmc AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?
    Madhumita Dandapani
    College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem Soc Trans 41:687-93. 2013
  8. pmc LKB1 and AMPK and the cancer-metabolism link - ten years after
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    BMC Biol 11:36. 2013
  9. doi request reprint Metformin-acting through cyclic AMP as well as AMP?
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Cell Metab 17:313-4. 2013
  10. doi request reprint The LKB1-AMPK pathway-friend or foe in cancer?
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Cancer Cell 23:131-2. 2013

Detail Information

Publications106 found, 100 shown here

  1. doi request reprint A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
    Mhairi C Towler
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Biochem J 416:1-14. 2008
    ..These results identify a previously undetected variant of LKB1, and suggest that it has a crucial role in spermiogenesis and male fertility...
  2. ncbi request reprint AMP-Activated Protein Kinase: Maintaining Energy Homeostasis at the Cellular and Whole-Body Levels
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, United Kingdom email
    Annu Rev Nutr 34:31-55. 2014
    ..AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as "nutraceuticals." ..
  3. pmc C-terminal phosphorylation of LKB1 is not required for regulation of AMP-activated protein kinase, BRSK1, BRSK2, or cell cycle arrest
    Sarah Fogarty
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 284:77-84. 2009
    ..Our results do not support the idea that phosphorylation of Ser-431 increases the ability of LKB1 to phosphorylate downstream targets...
  4. pmc Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP
    Sarah Fogarty
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U K
    Biochem J 426:109-18. 2010
    ..This is consistent with the effect of AMP on phosphorylation of Thr172 being due to inhibition of dephosphorylation, and confirms that the effect of AMP is independent of the upstream kinase utilized...
  5. pmc AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation
    Graeme J Gowans
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Cell Metab 18:556-66. 2013
    ..Thus, AMP is a true physiological regulator of AMPK, and allosteric regulation is an important component of the overall activation mechanism...
  6. pmc AMPK: a target for drugs and natural products with effects on both diabetes and cancer
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Diabetes 62:2164-72. 2013
    ..Interestingly, there is evidence that both metformin and aspirin provide some protection against development of cancer in humans, and whether AMPK might be involved in these effects is also discussed. ..
  7. pmc AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?
    Madhumita Dandapani
    College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem Soc Trans 41:687-93. 2013
    ..Evidence supporting this view is discussed, including our findings that AMPK is activated by the classic anti-inflammatory drug salicylate...
  8. pmc LKB1 and AMPK and the cancer-metabolism link - ten years after
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    BMC Biol 11:36. 2013
    ..This finding represented the first clear link between AMPK and cancer. Here we briefly discuss how this discovery came about, and describe some of the insights, especially into the role of AMPK in cancer, that have followed from it...
  9. doi request reprint Metformin-acting through cyclic AMP as well as AMP?
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Cell Metab 17:313-4. 2013
    ..Several targets to account for its therapeutic effects have been proposed, but a recent paper suggests a novel mechanism in which it antagonizes the cyclic AMP-dependent effects of glucagon on hepatic glucose production...
  10. doi request reprint The LKB1-AMPK pathway-friend or foe in cancer?
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Cancer Cell 23:131-2. 2013
    ..In this issue of Cancer Cell, Shackelford and colleagues show, paradoxically, that biguanides are more effective in the treatment of mouse tumors that lack a functional LKB1-AMPK pathway...
  11. ncbi request reprint AMP-activated protein kinase: a target for drugs both ancient and modern
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    Chem Biol 19:1222-36. 2012
    ..We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines...
  12. ncbi request reprint Adenosine monophosphate-activated protein kinase: a central regulator of metabolism with roles in diabetes, cancer, and viral infection
    D G Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Cold Spring Harb Symp Quant Biol 76:155-64. 2011
    ..A similar phenomenon occurs during viral infection. If we can establish how down-regulation occurs in tumors and virus-infected cells, there may be therapeutic avenues to reverse these effects...
  13. ncbi request reprint AMPK: a nutrient and energy sensor that maintains energy homeostasis
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Nat Rev Mol Cell Biol 13:251-62. 2012
    ..Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability...
  14. pmc Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
    ..We recently showed that LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta...
  15. pmc Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation
    Simon A Hawley
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Cell Metab 11:554-65. 2010
    ..Our approaches distinguish at least six different mechanisms for AMPK activation and confirm that the widely used antidiabetic drug metformin activates AMPK by inhibiting mitochondrial respiration...
  16. pmc The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor
    Andrew McBride
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Cell Metab 9:23-34. 2009
    ..Our results suggest the hypothesis that AMPK, as well as monitoring immediate energy availability by sensing AMP/ATP, may also be able to sense the status of cellular energy reserves in the form of glycogen...
  17. pmc Histological evaluation of AMPK signalling in primary breast cancer
    Sirwan M Hadad
    Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee, UK
    BMC Cancer 9:307. 2009
    ..The aim of this study was to examine the state of AMPK phosphorylation histologically in primary breast cancer in relation to clinical and pathological parameters...
  18. ncbi request reprint The AMP-activated protein kinase pathway--new players upstream and downstream
    D Grahame Hardie
    Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    J Cell Sci 117:5479-87. 2004
    ....
  19. ncbi request reprint AMP-activated protein kinase as a drug target
    D Grahame Hardie
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    Annu Rev Pharmacol Toxicol 47:185-210. 2007
    ..AMPK activators also now have potential as anticancer drugs...
  20. pmc AMP-activated protein kinase--development of the energy sensor concept
    D Grahame Hardie
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB CIR Complex, Dow Street, Dundee DD1 5EH, Scotland, UK
    J Physiol 574:7-15. 2006
    ..Low levels of activation of AMPK are likely to play a role in the current global rise in obesity and Type 2 diabetes, and AMPK is the target for the widely used antidiabetic drug metformin...
  21. ncbi request reprint A neural protection racket: AMPK and the GABA(B) receptor
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Neuron 53:159-62. 2007
    ..A study by Kuramoto and colleagues in this issue of Neuron favors the idea that AMPK activation is neuroprotective, and suggests a potential mechanism for this effect involving phosphorylation of the GABA(B) receptor...
  22. ncbi request reprint AMPK: a key sensor of fuel and energy status in skeletal muscle
    D Grahame Hardie
    Division of Molecular Physiology, University of Dundee, Dundee, Scotland
    Physiology (Bethesda) 21:48-60. 2006
    ..Recent work using a muscle-specific knockout of the upstream kinase, LKB1, has confirmed that the LKB1-->AMPK cascade is the signaling pathway responsible for many of these effects...
  23. ncbi request reprint New roles for the LKB1-->AMPK pathway
    D Grahame Hardie
    Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee, DD1 4HN, Scotland, UK
    Curr Opin Cell Biol 17:167-73. 2005
    ..AMPK inhibits the TOR (target of rapamycin) pathway by phosphorylating TSC2, thus inhibiting cell growth during times of stress. AMPK is also a target for adipokines that regulate energy balance at the whole-body level...
  24. ncbi request reprint AMP-activated protein kinase: a master switch in glucose and lipid metabolism
    D Grahame Hardie
    Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Rev Endocr Metab Disord 5:119-25. 2004
  25. pmc AMP-activated protein kinase: the guardian of cardiac energy status
    D Grahame Hardie
    Division of Molecular Physiology, Faculty of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    J Clin Invest 114:465-8. 2004
  26. ncbi request reprint Biochemistry. Balancing cellular energy
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Science 315:1671-2. 2007
  27. ncbi request reprint AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Nat Rev Mol Cell Biol 8:774-85. 2007
    ..Surprisingly, recent results indicate that the AMPK system is also important in functions that go beyond the regulation of energy homeostasis, such as the maintenance of cell polarity in epithelial cells...
  28. pmc AMPK and SNF1: Snuffing Out Stress
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Cell Metab 6:339-40. 2007
    ..Three new papers providing structural information on mammalian and yeast AMPK homologs give insights into the binding of the regulatory nucleotides AMP and ATP and how mutations are associated with cardiac glycogen storage disorders...
  29. pmc AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function
    D Grahame Hardie
    Division of Cell Signalling and Immunology, College of Life Science, University of Dundee, Scotland, United Kingdom
    Genes Dev 25:1895-908. 2011
    ..Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth...
  30. doi request reprint AMP-activated protein kinase: also regulated by ADP?
    D Grahame Hardie
    College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Trends Biochem Sci 36:470-7. 2011
    ..We also discuss the role of the carbohydrate-binding module on the β subunit and the mechanisms by which it is activated by drugs and xenobiotics such as metformin and resveratrol...
  31. doi request reprint Sensing of energy and nutrients by AMP-activated protein kinase
    D Grahame Hardie
    College of Life Sciences, University of Dundee, United Kingdom
    Am J Clin Nutr 93:891S-6. 2011
    ..Most of these agents activate AMPK because they inhibit mitochondrial function...
  32. doi request reprint AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer
    D Grahame Hardie
    College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem Soc Trans 39:1-13. 2011
    ..However, if we can identify the various mechanisms by which this occurs, we may be able to find ways of overcoming it...
  33. doi request reprint Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism
    D Grahame Hardie
    College of Life Sciences, University of Dundee, Dundee, UK
    Proc Nutr Soc 70:92-9. 2011
    ..We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished...
  34. ncbi request reprint AMPK: a key regulator of energy balance in the single cell and the whole organism
    D G Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, UK
    Int J Obes (Lond) 32:S7-12. 2008
    ..Novel drugs activating AMPK may also have potential for the treatment of obesity...
  35. doi request reprint AMPK and Raptor: matching cell growth to energy supply
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Science, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Mol Cell 30:263-5. 2008
    ..2008) suggest a novel mechanism by which AMPK signals to mTOR, and they provide new insight into how information about cellular energy status is fed into decisions about cell growth and proliferation...
  36. ncbi request reprint How I became a biochemist
    D Grahame Hardie
    Division of Molecular Physiology, University of Dundee, Dundee, Scotland, UK
    IUBMB Life 59:793-6. 2007
  37. ncbi request reprint Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    FEBS Lett 582:81-9. 2008
    ..However, activating mutations in AMPK can cause heart disease, and it will be important to look for adverse effects in the heart...
  38. ncbi request reprint AMP-activated protein kinase: a key system mediating metabolic responses to exercise
    D Grahame Hardie
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Med Sci Sports Exerc 36:28-34. 2004
    ....
  39. ncbi request reprint The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell?
    D G Hardie
    Biochemistry Department, University, Dundee, Scotland, United Kingdom
    Annu Rev Biochem 67:821-55. 1998
    ..SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress...
  40. ncbi request reprint The AMP-activated protein kinase--fuel gauge of the mammalian cell?
    D G Hardie
    Biochemistry Department, The University, Dundee, UK
    Eur J Biochem 246:259-73. 1997
    ..AMPK/SNF1 homologues are found in higher plants, and this protein-kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress...
  41. ncbi request reprint Management of cellular energy by the AMP-activated protein kinase system
    D Grahame Hardie
    Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    FEBS Lett 546:113-20. 2003
    ..A survey of the range of downstream targets for this important signalling pathway is presented...
  42. pmc AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge
    D G Hardie
    Biochemistry Department, Dundee University, MSI WTB complex, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 338:717-22. 1999
    ....
  43. ncbi request reprint Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase
    S A Hawley
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, United Kingdom
    J Biol Chem 271:27879-87. 1996
    ..A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., and Hardie, D. G. (1995) J. Biol. Chem. 270, 27186-27191)...
  44. ncbi request reprint Metabolic control: a new solution to an old problem
    D G Hardie
    Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Scotland, UK
    Curr Biol 10:R757-9. 2000
    ..A novel mechanism has now been discovered, involving the AMP-activated protein kinase cascade, that can account for the Pasteur effect in ischaemic heart muscle...
  45. ncbi request reprint Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status
    D Grahame Hardie
    Division of Molecular Physiology, University of Dundee, Wellcome Trust Biocentre, Dundee DD1 5EH, Scotland, United Kingdom
    Endocrinology 144:5179-83. 2003
    ....
  46. ncbi request reprint Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase
    D G Hardie
    Division of Molecular Physiology, School of Life Sciences, Dundee University, UK
    Biochem Soc Trans 30:1064-70. 2002
    ..This is abolished when expression of DmAMPK is ablated using an RNA interference approach, proving that DmAMPK is necessary for phosphorylation of DmACC in response to ATP depletion...
  47. ncbi request reprint AMP-activated protein kinase: the energy charge hypothesis revisited
    D G Hardie
    Wellcome Trust Biocentre, Division of Molecular Physiology, Dundee University, Dundee, Scotland, UK
    Bioessays 23:1112-9. 2001
    ..Dominant mutations in regulatory subunit isoforms (gamma2 and gamma3) of AMPK, which appear to increase the basal activity in the absence of AMP, lead to hypertrophy of cardiac and skeletal muscle respectively...
  48. ncbi request reprint AMP-activated protein kinase in metabolic control and insulin signaling
    Mhairi C Towler
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Circ Res 100:328-41. 2007
    ..It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome...
  49. ncbi request reprint Biochemical characterization of two forms of 3-hydroxy-3-methylglutaryl-CoA reductase kinase from cauliflower (Brassica oleracia)
    K L Ball
    Biochemistry Department, The University, Dundee, Scotland
    Eur J Biochem 219:743-50. 1994
    ..Form B does not appear to be a proteolytic fragment of form A, and we therefore propose that it represents a closely related member of the same protein kinase sub-family...
  50. ncbi request reprint Analysis of sites phosphorylated on acetyl-CoA carboxylase in response to insulin in isolated adipocytes. Comparison with sites phosphorylated by casein kinase-2 and the calmodulin-dependent multiprotein kinase
    T A Haystead
    Biochemistry Department, Dundee University, Scotland
    Eur J Biochem 175:347-54. 1988
    ..The function of this modification is not clear, since phosphorylation by casein kinase-2 has no direct effect on acetyl-CoA carboxylase activity...
  51. ncbi request reprint AMP-activated protein kinase--an archetypal protein kinase cascade?
    D G Hardie
    Biochemistry Department, University, Dundee, Scotland, UK
    Bioessays 14:699-704. 1992
    ..This system therefore represents an early eukaryotic protein kinase cascade, which is unique in that it is regulated by intracellular metabolites rather than extracellular signals or cell cycle events...
  52. pmc Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver
    P R Clarke
    Protein Phosphorylation Group, Department of Biochemistry, The University, Dundee, Scotland, UK
    EMBO J 9:2439-46. 1990
    ..We have also identified by amino acid sequencing the N-terminus of the catalytic fragment, which corresponds to residue 423 of the human enzyme...
  53. ncbi request reprint Activation of rat liver AMP-activated protein kinase by kinase kinase in a purified, reconstituted system. Effects of AMP and AMP analogues
    J Weekes
    Biochemistry Department, The University, Dundee, Scotland
    Eur J Biochem 219:751-7. 1994
    ..These results suggest that both the allosteric effect of AMP, and the promotion of phosphorylation and activation by the kinase kinase, are due to binding of AMP to a single site on the kinase...
  54. ncbi request reprint Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase
    M R Munday
    MRC Protein Phosphorylation Group, Biochemistry Department, University of Dundee, Tayside, Scotland
    Eur J Biochem 175:331-8. 1988
    ..They also open the way to experiments which could establish the physiological roles of these protein kinases in the control of fatty acid synthesis...
  55. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    ..Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function...
  56. doi request reprint Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer
    S Fogarty
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochim Biophys Acta 1804:581-91. 2010
    ..Thus, activators of AMPK could have potential as novel therapeutics both for metabolic disorders and for cancer, which together constitute two of the most prevalent groups of diseases worldwide...
  57. ncbi request reprint AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line
    Franck Rencurel
    Biomedical Research Centre and Cancer Research UK Molecular Pharmacology Unit, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 280:4367-73. 2005
    ..Our data strongly support a role for AMPK in the PB induction of CYP2B gene expression and provide new insights into the regulation of gene expression by barbiturate drugs...
  58. ncbi request reprint Protein kinase substrate recognition studied using the recombinant catalytic domain of AMP-activated protein kinase and a model substrate
    John W Scott
    Division of Molecular Physiology, School of Life Sciences and Wellcome Trust Biocentre, Dundee University, Scotland, UK
    J Mol Biol 317:309-23. 2002
    ..Although based on modelling rather than a determined structure, this represents one of the most detailed studies of the interaction between a kinase and its substrate achieved to date...
  59. doi request reprint AMP-activated protein kinase--a sensor of glycogen as well as AMP and ATP?
    A McBride
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dow Street, Dundee, UK
    Acta Physiol (Oxf) 196:99-113. 2009
    ..The literature concerning AMPK, glycogen structure and glycogen-binding proteins that led us to this concept is reviewed...
  60. ncbi request reprint Similar substrate recognition motifs for mammalian AMP-activated protein kinase, higher plant HMG-CoA reductase kinase-A, yeast SNF1, and mammalian calmodulin-dependent protein kinase I
    S Dale
    Department of Biochemistry, The University, Dundee, Scotland, UK
    FEBS Lett 361:191-5. 1995
    ....
  61. ncbi request reprint Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes
    J G Gillespie
    Department of Biochemistry, The University, Dundee, Scotland, UK
    FEBS Lett 306:59-62. 1992
    ....
  62. ncbi request reprint Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase
    Simon A Hawley
    Division of Molecular Physiology University of Dundee, Dundee, Scotland, United Kingdom
    Cell Metab 2:9-19. 2005
    ..Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta...
  63. ncbi request reprint Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles
    Paula E Durante
    Division of Molecular Physiology, School of Life Sciences, Dundee University, Wellcome Trust Biocentre, Dundee, DD1 5EH Scotland, UK
    Am J Physiol Endocrinol Metab 283:E178-86. 2002
    ..There was a threefold increase in expression of gamma 3 after training in red quadriceps only. Our results suggest that gamma 3 might have a special role in the adaptation to endurance exercise in muscles utilizing oxidative metabolism...
  64. ncbi request reprint The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism
    Simon A Hawley
    Division of Molecular Physiology, School of Life Sciences and Wellcome Trust Biocentre, Dundee University, Dundee, Scotland, UK
    Diabetes 51:2420-5. 2002
    ..Our results also show that AMPK can be activated by mechanisms other than changes in the cellular AMP-to-ATP ratio...
  65. pmc CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations
    John W Scott
    Division of Molecular Physiology, Faculty of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Scotland, United Kingdom
    J Clin Invest 113:274-84. 2004
    ..This shows that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a newly identified class of binding domain for adenosine derivatives...
  66. ncbi request reprint Cloning of DNA encoding a catalytic subunit of SNF1-related protein kinase-1 (SnRK1-alpha1), and immunological analysis of multiple forms of the kinase, in spinach leaf
    R M Crawford
    Biochemistry Department, Dundee University, UK
    Plant Mol Biol 45:731-41. 2001
    ..A 35 kDa polypeptide recognized by an antibody against the putative Arabidopsis beta2 subunit co-precipitates with HRK-C, but not HRK-A or D...
  67. ncbi request reprint A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias
    Emma R Hudson
    Division of Molecular Physiology, Faculty of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dow Street, Scotland, United Kingdom
    Curr Biol 13:861-6. 2003
    ..These may be related to the abnormal glycogen storage bodies seen in heart disease patients with gamma2 mutations...
  68. pmc Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR
    Kathryn M Geraghty
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 407:231-41. 2007
    ..Thus, although AS160 is a common target of insulin, IGF-1, EGF, PMA and AICAR, these stimuli induce distinctive patterns of phosphorylation and 14-3-3 binding, mediated by at least four protein kinases...
  69. ncbi request reprint PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway
    Kanchana Dokladda
    Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    FEBS Lett 579:236-40. 2005
    ..These results suggest the need for caution in interpreting experiments conducted using U0126 and PD98059...
  70. pmc Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the gamma subunit
    John W Scott
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, UK
    EMBO J 26:806-15. 2007
    ..Binding of AMP causes a conformational change that prevents this interaction and relieves the inhibition. We present several lines of evidence supporting this hypothesis...
  71. ncbi request reprint AICA riboside both activates AMP-activated protein kinase and competes with adenosine for the nucleoside transporter in the CA1 region of the rat hippocampus
    Anne E Gadalla
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, UK
    J Neurochem 88:1272-82. 2004
    ..Caution should therefore be exercised in ascribing an effect of AICA riboside to AMPK activation, especially in systems where inhibition of adenosine re-uptake has physiological consequences...
  72. pmc Normal hypertrophy accompanied by phosphoryation and activation of AMP-activated protein kinase alpha1 following overload in LKB1 knockout mice
    Sean L McGee
    Functional Molecular Biology Lab, Division of Molecular Physiology, University of Dundee, Sir James Black Centre, Dow Street, Dundee DD1 5EH, UK
    J Physiol 586:1731-41. 2008
    ....
  73. ncbi request reprint Regulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase
    D G Hardie
    Biochemistry Department, The University, Dundee, U K
    Biochim Biophys Acta 1123:231-8. 1992
  74. pmc A homologue of AMP-activated protein kinase in Drosophila melanogaster is sensitive to AMP and is activated by ATP depletion
    David A Pan
    Division of Molecular Physiology, School of Life Sciences and Wellcome Trust Biocentre, Dundee University, Dundee DD1 5EH, Scotland, U K
    Biochem J 367:179-86. 2002
    ..Drosophila cells now represent an attractive system to study this pathway, because of the small, well-defined genome and the ability to ablate expression of specific gene products using interfering dsRNAs...
  75. ncbi request reprint Analysis of the LKB1-STRAD-MO25 complex
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland
    J Cell Sci 117:6365-75. 2004
    ..Taken together, our findings reinforce the functional importance of the binding of LKB1 to STRAD, and provide a greater understanding of the mechanism by which LKB1 is regulated and activated through its interaction with STRAD and MO25...
  76. ncbi request reprint Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR
    Kei Sakamoto
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Scotland, UK
    Am J Physiol Endocrinol Metab 287:E310-7. 2004
    ..They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases...
  77. ncbi request reprint 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men
    Daniel J Cuthbertson
    Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK
    Diabetes 56:2078-84. 2007
    ..3 +/- 0.6 to 10 +/- 0.6 mg x kg(-1) x min(-1) (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal...
  78. doi request reprint Small molecules can have big effects on endurance
    Keith Baar
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Nat Chem Biol 4:583-4. 2008
  79. pmc Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes
    Peter Tamas
    Division of Cell Biology and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Exp Med 203:1665-70. 2006
    ..Moreover, AMPK does not just react to cellular energy depletion but also anticipates it...
  80. ncbi request reprint Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex
    Catherine M Sutherland
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    Curr Biol 13:1299-305. 2003
    ..In both cases, activation requires phosphorylation at a conserved threonine residue within the activation loop of the kinase domain, but identifying the upstream kinase(s) responsible for this has been a challenging, unsolved problem...
  81. ncbi request reprint Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes
    Kurt Højlund
    Diabetes Research Centre, University of Southern Denmark and Department of Endocrinology, Odense University Hospital, Kloevervaenget 6, DK 5000 Odense C, Denmark
    Diabetes 52:1393-402. 2003
    ..This phosphorylation abnormality likely caused the impaired GS activation and glucose storage, thereby contributing to skeletal muscle insulin resistance, and may therefore play a pathophysiological role in type 2 diabetes...
  82. ncbi request reprint Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase
    Blerina Kola
    Department of Endocrinology, William Harvey Research Institute, Barts and the London Medical School, London EC1M 6BQ, United Kingdom
    J Biol Chem 280:25196-201. 2005
    ..Our data demonstrate that AMPK not only links the orexigenic effects of endocannabinoids and ghrelin in the hypothalamus but also their effects on the metabolism of peripheral tissues...
  83. ncbi request reprint Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle
    Agnieszka Dobrzyn
    Dept of Biochemistry, Univ of Wisconsin, 433 Babcock Dr, Madison, WI 53706, USA
    Am J Physiol Endocrinol Metab 288:E599-607. 2005
    ..Taken together, these results indicate that SCD1 deficiency reduces ceramide synthesis by decreasing SPT expression and increasing the rate of beta-oxidation in oxidative muscles...
  84. ncbi request reprint Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis
    Clara Prats
    Copenhagen Muscle Research Centre, University of Copenhagen, Denmark
    J Biol Chem 280:23165-72. 2005
    ..Here, we present evidence of a new regulatory mechanism of skeletal muscle glycogen metabolism based on glycogen enzyme intracellular compartmentalization...
  85. ncbi request reprint 5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle
    Christian Frøsig
    Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark
    Am J Physiol Endocrinol Metab 286:E411-7. 2004
    ..Except for the increase in gamma1 protein, all observed adaptations to training could be ascribed to local contraction-induced mechanisms, since they did not occur in the contralateral untrained muscle...
  86. ncbi request reprint The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading
    Sebastian B Jørgensen
    Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
    Diabetes 53:3074-81. 2004
    ..The fact that alpha2-AMPK is a GS kinase that inactivates GS while simultaneously activating glucose transport suggests that a balanced view on the suitability for AMPK as an antidiabetic drug target should be taken...
  87. pmc Biochemical characterization of the tobacco 42-kD protein kinase activated by osmotic stress
    Anna Kelner
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02 106 Warsaw, Poland
    Plant Physiol 136:3255-65. 2004
    ..The enzyme activity was not modulated by 5'-AMP. To our knowledge, these results represent the first detailed biochemical characterization of a kinase of the SnRK2 family...
  88. pmc Regulation of hormone-sensitive lipase activity and Ser563 and Ser565 phosphorylation in human skeletal muscle during exercise
    Carsten Roepstorff
    The Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark
    J Physiol 560:551-62. 2004
    ..Apparently, HSL Ser565 phosphorylation by AMPK during exercise had no effect on HSL activity. Alternatively, other factors including ERK may have counterbalanced any effect of AMPK on HSL activity...
  89. pmc Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver
    Pawel Dobrzyn
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 101:6409-14. 2004
    ..001) thereby stimulating the oxidation of mitochondrial palmitoyl-CoA. Our results identify AMPK as a mediator of increased fatty acid oxidation in liver of SCD1-deficient mice...
  90. ncbi request reprint AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes
    Kurt Højlund
    Department of Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark
    Am J Physiol Endocrinol Metab 286:E239-44. 2004
    ..These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity...
  91. pmc Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells
    Alison M Woollhead
    Department Basic Medical Sciences, Physiology, St Georges Hospital Medical School, University of London, London SW17 0RE, UK
    J Physiol 566:781-92. 2005
    ..These are the first studies to provide a cellular signalling mechanism for the action of phenformin on ion transport processes, and also the first studies showing AMPK as a regulator of Na+ absorption in the lung...
  92. ncbi request reprint AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
    Barbara B Kahn
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 1:15-25. 2005
    ..Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes...
  93. ncbi request reprint Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?
    A Mark Evans
    Division of Biomedical Sciences, School of Biology, Bute Building, University of St Andrews, St Andrews, Fife KY16 9TS, United Kingdom
    J Biol Chem 280:41504-11. 2005
    ..Thus, metabolic sensing by AMP-activated protein kinase may mediate chemotransduction by hypoxia...
  94. pmc Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase
    Olga Göransson
    Division for Diabetes, Metabolism and Endocrinology, Department of Experimental Medical Science, Lund University, Lund, Sweden
    J Biol Chem 282:32549-60. 2007
    ..We propose that this direct and specific AMPK activator will be a valuable experimental tool to understand the physiological roles of AMPK...
  95. ncbi request reprint Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase
    Hasan O Akman
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA, and Department of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
    Pediatr Res 62:499-504. 2007
    ..Our studies confirm that mutations in PRKAG2 can cause fatal infantile cardiomyopathy, often associated with apparent PHK deficiency...
  96. pmc Role of 5'AMP-activated protein kinase in glycogen synthase activity and glucose utilization: insights from patients with McArdle's disease
    Jakob N Nielsen
    Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Denmark
    J Physiol 541:979-89. 2002
    ....
  97. ncbi request reprint Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise
    Carsten Roepstorff
    The Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
    Am J Physiol Endocrinol Metab 291:E1106-14. 2006
    ..The higher basal IMTG content in women compared with men is therefore the best candidate to explain the higher IMTG net hydrolysis during exercise in women...
  98. ncbi request reprint Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK)
    Kay Barnes
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    J Cell Sci 115:2433-42. 2002
    ..These enzymes, which have been implicated in stress-regulated pathways in other cell types, are therefore unlikely to play a role in transport regulation by stress in Clone 9 cells...
  99. ncbi request reprint Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle
    Hua Ai
    Copenhagen Muscle Research Centre, Department of Medical Physiology, Panum Institute, DK 2200, Copenhagen, Denmark
    Am J Physiol Endocrinol Metab 282:E1291-300. 2002
    ..In conclusion, AICAR-stimulated glucose transport varies with muscle fiber type and nutritional state. AMPK is unlikely to be the sole mediator of contraction-stimulated glucose transport...
  100. pmc Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis
    Richard M Reznick
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell Metab 5:151-6. 2007
    ..These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging...
  101. ncbi request reprint A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes
    Stephen M Downs
    Biology Department, Marquette University, 530 N 15 Street, Milwaukee, WI 53233, USA
    Dev Biol 245:200-12. 2002
    ..It is concluded that phosphodiesterase-generated AMP may serve as a transducer of the meiotic induction process through activation of AMPK...