AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy

The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all eukaryotic cells. The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels. When energy status is compromised, the system activates catabolic pathways and switches off protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. 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.

[1]  M. Caplan,et al.  AMP-activated protein kinase regulates the assembly of epithelial tight junctions , 2006, Proceedings of the National Academy of Sciences.

[2]  M. Carlson,et al.  The Snf1 protein kinase and its activating subunit, Snf4, interact with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex , 1997, Molecular and cellular biology.

[3]  Y. Uchijima,et al.  Glycogen debranching enzyme association with beta-subunit regulates AMP-activated protein kinase activity. , 2005, American journal of physiology. Endocrinology and metabolism.

[4]  Jérôme Boudeau,et al.  Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade , 2003, Journal of biology.

[5]  A. Sharff,et al.  Structure of a CBS-domain pair from the regulatory gamma1 subunit of human AMPK in complex with AMP and ZMP. , 2007, Acta crystallographica. Section D, Biological crystallography.

[6]  D. Hardie,et al.  Elm1p Is One of Three Upstream Kinases for the Saccharomyces cerevisiae SNF1 Complex , 2003, Current Biology.

[7]  B. Kemp,et al.  Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. , 1994, The Journal of biological chemistry.

[8]  P. Roach,et al.  Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent Kinase Pho85p , 2001, Molecular and Cellular Biology.

[9]  B. Burwinkel,et al.  Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. , 2005, American journal of human genetics.

[10]  J. Scott,et al.  Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. , 1994, The Journal of biological chemistry.

[11]  David Carling,et al.  Supplemental Data LKB 1 Is the Upstream Kinase in the AMP-Activated Protein Kinase Cascade , 2003 .

[12]  N. Fujii,et al.  Distinct Signals Regulate AS160 Phosphorylation in Response to Insulin, AICAR, and Contraction in Mouse Skeletal Muscle , 2006, Diabetes.

[13]  B. Kemp,et al.  Active site-directed protein regulation , 1999, Nature.

[14]  D. Tzamarias,et al.  The Snf1 kinase controls glucose repression in yeast by modulating interactions between the Mig1 repressor and the Cyc8‐Tup1 co‐repressor , 2004, EMBO reports.

[15]  David Carling,et al.  The Anti-diabetic Drugs Rosiglitazone and Metformin Stimulate AMP-activated Protein Kinase through Distinct Signaling Pathways* , 2002, The Journal of Biological Chemistry.

[16]  C. Bauvy,et al.  AMP-activated Protein Kinase and the Regulation of Autophagic Proteolysis* , 2006, Journal of Biological Chemistry.

[17]  B. Kemp,et al.  AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling , 2007, Circulation research.

[18]  Kei Sakamoto,et al.  LKB1-dependent signaling pathways. , 2006, Annual review of biochemistry.

[19]  S. Hawley,et al.  5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? , 1995, European journal of biochemistry.

[20]  Jérôme Boudeau,et al.  LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1 , 2004, The EMBO journal.

[21]  D. Carling,et al.  Thrombin Activates AMP-Activated Protein Kinase in Endothelial Cells via a Pathway Involving Ca 2 /Calmodulin-Dependent , 2006 .

[22]  D. Hardie,et al.  5′‐AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP‐activated protein kinase. Studies using bacterially expressed human protein phosphatase‐2Cα and native bovine protein phosphatase‐2Ac , 1995, FEBS letters.

[23]  Russell G. Jones,et al.  AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. , 2005, Molecular cell.

[24]  D. Hardie,et al.  CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. , 2004, The Journal of clinical investigation.

[25]  G. Shulman,et al.  AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Carlson,et al.  Mammalian TAK1 Activates Snf1 Protein Kinase in Yeast and Phosphorylates AMP-activated Protein Kinase in Vitro* , 2006, Journal of Biological Chemistry.

[27]  B. Kemp,et al.  AMP-activated Protein Kinase β Subunit Tethers α and γ Subunits via Its C-terminal Sequence (186–270)* , 2005, Journal of Biological Chemistry.

[28]  K. Inoki,et al.  TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling , 2002, Nature Cell Biology.

[29]  B. Viollet,et al.  The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading. , 2004, Diabetes.

[30]  Margaret S. Wu,et al.  Role of AMP-activated protein kinase in mechanism of metformin action. , 2001, The Journal of clinical investigation.

[31]  B. Kemp,et al.  Intrasteric control of AMPK via the γ1 subunit AMP allosteric regulatory site , 2004 .

[32]  A. Means,et al.  The Ca2+/Calmodulin-dependent Protein Kinase Kinases Are AMP-activated Protein Kinase Kinases* , 2005, Journal of Biological Chemistry.

[33]  S. Berger,et al.  Structure and dimerization of the kinase domain from yeast Snf1, a member of the Snf1/AMPK protein family. , 2006, Structure.

[34]  J. Seidman,et al.  Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. , 2002, The Journal of clinical investigation.

[35]  D. James,et al.  Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States , 2006, Diabetes.

[36]  A. Sim,et al.  The AMP-activated protein kinase: a multisubstrate regulator of lipid metabolism , 1989 .

[37]  David Carling,et al.  Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[38]  David Carling,et al.  The SNF1 kinase complex from Saccharomyces cerevisiae phosphorylates the transcriptional repressor protein Mig1p in vitro at four sites within or near regulatory domain 1 , 1999, FEBS letters.

[39]  Uwe Riek,et al.  Dissecting the Role of 5′-AMP for Allosteric Stimulation, Activation, and Deactivation of AMP-activated Protein Kinase* , 2006, Journal of Biological Chemistry.

[40]  J. Ha,et al.  Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. , 2007, Cancer letters.

[41]  Ferhaan Ahmad,et al.  Transgenic Mice Overexpressing Mutant PRKAG2 Define the Cause of Wolff-Parkinson-White Syndrome in Glycogen Storage Cardiomyopathy , 2003, Circulation.

[42]  M. Gorospe,et al.  AMP-Activated Kinase Regulates Cytoplasmic HuR , 2002, Molecular and Cellular Biology.

[43]  D. Hardie,et al.  AMPK: a key sensor of fuel and energy status in skeletal muscle. , 2006, Physiology.

[44]  M. Gorospe,et al.  Increased AMP:ATP Ratio and AMP-activated Protein Kinase Activity during Cellular Senescence Linked to Reduced HuR Function* , 2003, Journal of Biological Chemistry.

[45]  Jun Hee Lee,et al.  Energy-dependent regulation of cell structure by AMP-activated protein kinase , 2007, Nature.

[46]  J. Seidman,et al.  AMP-Activated Protein Kinase in the Heart: Role During Health and Disease , 2007, Circulation research.

[47]  B. Kemp,et al.  AMPK β Subunit Targets Metabolic Stress Sensing to Glycogen , 2003, Current Biology.

[48]  Galina Polekhina,et al.  Structural basis for glycogen recognition by AMP-activated protein kinase. , 2005, Structure.

[49]  R. Roy,et al.  Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling , 2006, Development.

[50]  D. Hardie,et al.  5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? , 1995, European journal of biochemistry.

[51]  B. Kemp,et al.  Genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation. , 2007, American journal of physiology. Endocrinology and metabolism.

[52]  D. Hardie,et al.  AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. , 2005, Cell metabolism.

[53]  M. Febbraio,et al.  CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK , 2006, Nature Medicine.

[54]  D. Hardie,et al.  AMP-activated protein kinase as a drug target. , 2007, Annual review of pharmacology and toxicology.

[55]  C. Polge,et al.  SNF1/AMPK/SnRK1 kinases, global regulators at the heart of energy control? , 2007, Trends in plant science.

[56]  B. Viollet,et al.  A Conserved Sequence Immediately N-terminal to the Bateman Domains in AMP-activated Protein Kinase γ Subunits Is Required for the Interaction with the β Subunits* , 2007, Journal of Biological Chemistry.

[57]  K. Inoki,et al.  TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival , 2003, Cell.

[58]  D. Carling,et al.  Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. , 2007, The Biochemical journal.

[59]  Daniel St Johnston,et al.  A role for Drosophila LKB1 in anterior–posterior axis formation and epithelial polarity , 2003, Nature.

[60]  S. Hawley,et al.  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* , 1996, The Journal of Biological Chemistry.

[61]  L. Riechmann,et al.  An antibody VH domain with a lox‐Cre site integrated into its coding region: bacterial recombination within a single polypeptide chain , 1995, FEBS letters.

[62]  D. Hardie,et al.  A homologue of AMP-activated protein kinase in Drosophila melanogaster is sensitive to AMP and is activated by ATP depletion. , 2002, The Biochemical journal.

[63]  R. Terjung,et al.  Contraction-mediated phosphorylation of AMPK is lower in skeletal muscle of adenylate kinase-deficient mice. , 2006, Journal of applied physiology.

[64]  J. Apfeld,et al.  The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. , 2004, Genes & development.

[65]  L. Cantley,et al.  Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase , 2007, Proceedings of the National Academy of Sciences.

[66]  Hans C Clevers,et al.  Complete Polarization of Single Intestinal Epithelial Cells upon Activation of LKB1 by STRAD , 2004, Cell.

[67]  E. Schrödinger.  What Is Life , 1946 .

[68]  H. Ronne,et al.  Snf1‐related protein kinase 1 is needed for growth in a normal day–night light cycle , 2004, The EMBO journal.

[69]  T. Mäkelä,et al.  LKB 1 is a master kinase that activates 13 protein kinases of the AMPK subfamily , including the MARK / PAR-1 kinases , 2004 .

[70]  A. Bateman.  The structure of a domain common to archaebacteria and the homocystinuria disease protein. , 1997, Trends in biochemical sciences.

[71]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[72]  John M Asara,et al.  Insulin-stimulated Phosphorylation of a Rab GTPase-activating Protein Regulates GLUT4 Translocation* , 2003, The Journal of Biological Chemistry.

[73]  P. Puigserver,et al.  Resveratrol improves health and survival of mice on a high-calorie diet , 2006, Nature.

[74]  L. Goodyear,et al.  5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. , 1999, Diabetes.

[75]  A. Prescott,et al.  The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation. , 2006, The Biochemical journal.

[76]  R. Heath,et al.  Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. , 2005, Cell metabolism.

[77]  M. Kaminishi,et al.  Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole- 4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. , 2001, Biochemical and biophysical research communications.

[78]  D. Vertommen,et al.  Activation of AMP-Activated Protein Kinase Leads to the Phosphorylation of Elongation Factor 2 and an Inhibition of Protein Synthesis , 2002, Current Biology.

[79]  D. Hardie,et al.  Protein kinase substrate recognition studied using the recombinant catalytic domain of AMP-activated protein kinase and a model substrate. , 2002, Journal of molecular biology.

[80]  S. Dimauro,et al.  Fatal Infantile Cardiac Glycogenosis with Phosphorylase Kinase Deficiency and a Mutation in the γ2-Subunit of AMP-Activated Protein Kinase , 2007, Pediatric Research.

[81]  B. Viollet,et al.  AMPK-Mediated AS160 Phosphorylation in Skeletal Muscle Is Dependent on AMPK Catalytic and Regulatory Subunits , 2006, Diabetes.

[82]  J. James,et al.  A Novel Domain in AMP-Activated Protein Kinase Causes Glycogen Storage Bodies Similar to Those Seen in Hereditary Cardiac Arrhythmias , 2003, Current Biology.

[83]  B. Kemp,et al.  Functional Domains of the α1 Catalytic Subunit of the AMP-activated Protein Kinase* , 1998, The Journal of Biological Chemistry.

[84]  R. McCartney,et al.  Yeast Pak1 Kinase Associates with and Activates Snf1 , 2003, Molecular and Cellular Biology.

[85]  D. Hardie,et al.  Glucose repression/derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio , 1996, Current Biology.

[86]  C. Rogel-Gaillard,et al.  A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. , 2000, Science.

[87]  M. Carlson,et al.  A yeast gene that is essential for release from glucose repression encodes a protein kinase. , 1986, Science.

[88]  I. Tabata,et al.  Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. , 2002, Biochemical and biophysical research communications.

[89]  K. Kim,et al.  Regulation of rat liver acetyl-CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl-CoA carboxylase by the adenylate energy charge. , 1980, The Journal of biological chemistry.

[90]  D. Carling,et al.  Functional Analysis of Mutations in the γ2 Subunit of AMP-activated Protein Kinase Associated with Cardiac Hypertrophy and Wolff-Parkinson-White Syndrome* , 2002, The Journal of Biological Chemistry.

[91]  Mark Johnston,et al.  The nuclear exportin Msn5 is required for nuclear export of the Mig1 glucose repressor of Saccharomyces cerevisiae , 1999, Current Biology.

[92]  Gordon B. Mills,et al.  The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis , 2007, Nature Cell Biology.

[93]  A. Edelman,et al.  Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. , 2005, Cell metabolism.

[94]  H. Lodish,et al.  A Revised Model for AMP-activated Protein Kinase Structure , 2006, Journal of Biological Chemistry.

[95]  C. Proud,et al.  Role of mTOR signalling in the control of translation initiation and elongation by nutrients. , 2004, Current Topics in Microbiology and Immunology.

[96]  F. Ross,et al.  Regulation of AMP‐activated protein kinase by a pseudosubstrate sequence on the γ subunit , 2007 .

[97]  B. Pedersen,et al.  Interleukin-6 Regulation of AMP-Activated Protein Kinase , 2006, Diabetes.

[98]  Tao Pang,et al.  Conserved α-Helix Acts as Autoinhibitory Sequence in AMP-activated Protein Kinase α Subunits* , 2007, Journal of Biological Chemistry.

[99]  Lawrence Shapiro,et al.  Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase , 2007, Science.

[100]  J. Seidman,et al.  Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage. , 2007, The Journal of clinical investigation.

[101]  Shailendra Giri,et al.  5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside Inhibits Cancer Cell Proliferation in Vitro and in Vivo via AMP-activated Protein Kinase* , 2005, Journal of Biological Chemistry.

[102]  K. A. Quayle.  Regulation of rat liver acetyl CoA carboxylase , 1986 .

[103]  D. Hardie,et al.  Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. , 2004, American journal of physiology. Endocrinology and metabolism.