ENTRY ko04152 Pathway NAME AMPK signaling pathway DESCRIPTION AMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Several upstream kinases, including liver kinase B1 (LKB1), calcium/calmodulin kinase kinase-beta (CaMKK beta), and TGF-beta-activated kinase-1 (TAK-1), can activate AMPK by phosphorylating a threonine residue on its catalytic alpha-subunit. Once activated, AMPK leads to a concomitant inhibition of energy-consuming biosynthetic pathways, such as protein, fatty acid and glycogen synthesis, and activation of ATP-producing catabolic pathways, such as fatty acid oxidation and glycolysis. CLASS Environmental Information Processing; Signal transduction PATHWAY_MAP ko04152 AMPK signaling pathway DBLINKS GO: 2000479 ORTHOLOGY K04427 mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25] K07298 serine/threonine-protein kinase 11 [EC:2.7.11.1] K08272 calcium binding protein 39 K08271 STE20-related kinase adapter protein alpha K17532 STE20-related kinase adapter protein beta K05424 leptin K05062 leptin receptor K07359 calcium/calmodulin-dependent protein kinase kinase 2 [EC:2.7.11.17] K04135 adrenergic receptor alpha-1A K07296 adiponectin K07297 adiponectin receptor K07198 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K07199 5'-AMP-activated protein kinase, regulatory beta subunit K07200 5'-AMP-activated protein kinase, regulatory gamma subunit K19028 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 1 [EC:2.7.1.105 3.1.3.46] K19029 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2 [EC:2.7.1.105 3.1.3.46] K01103 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 3 [EC:2.7.1.105 3.1.3.46] K19030 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 4 [EC:2.7.1.105 3.1.3.46] K03841 fructose-1,6-bisphosphatase I [EC:3.1.3.11] K00850 6-phosphofructokinase 1 [EC:2.7.1.11] K07292 hepatocyte nuclear factor 4-alpha K01084 glucose-6-phosphatase [EC:3.1.3.9] K01596 phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32] K16333 CREB-regulated transcription coactivator 2 K05870 cyclic AMP-responsive element-binding protein 1 K09048 cyclic AMP-responsive element-binding protein 3 K09047 cyclic AMP-responsive element-binding protein 5 K07202 alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha K13088 ELAV-like protein 1 K04503 G1/S-specific cyclin-D1 K06627 cyclin-A K08292 elongation factor 2 kinase [EC:2.7.11.20] K03234 elongation factor 2 K07201 forkhead box protein O1 K09408 forkhead box protein O3 K11411 NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286] K07191 MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 4 K00693 glycogen synthase [EC:2.4.1.11] K07188 hormone-sensitive lipase [EC:3.1.1.79] K00021 hydroxymethylglutaryl-CoA reductase (NADPH) [EC:1.1.1.34] K07197 sterol regulatory element-binding transcription factor 1 K00665 fatty acid synthase, animal type [EC:2.3.1.85] K11262 acetyl-CoA carboxylase / biotin carboxylase 1 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K00507 stearoyl-CoA desaturase (Delta-9 desaturase) [EC:1.14.19.1] K01946 acetyl-CoA carboxylase / biotin carboxylase 2 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K01578 malonyl-CoA decarboxylase [EC:4.1.1.9] K08765 carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21] K19523 carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21] K19524 carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21] K25893 cell death activator CIDE-A K04382 serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16] K03456 serine/threonine-protein phosphatase 2A regulatory subunit A K04354 serine/threonine-protein phosphatase 2A regulatory subunit B K11583 serine/threonine-protein phosphatase 2A regulatory subunit B'' K11584 serine/threonine-protein phosphatase 2A regulatory subunit B' K18341 TBC1 domain family member 1 K07877 Ras-related protein Rab-2A K07901 Ras-related protein Rab-8A K07903 Ras-related protein Rab-10 K07905 Ras-related protein Rab-11B K07881 Ras-related protein Rab-14 K05031 cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6] K06259 CD36 antigen K05459 insulin-like growth factor 1 K05087 insulin-like growth factor 1 receptor [EC:2.7.10.1] K04526 insulin K04527 insulin receptor [EC:2.7.10.1] K16172 insulin receptor substrate 1 K07187 insulin receptor substrate 2 K17445 insulin receptor substrate 3 K17446 insulin receptor substrate 4 K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta K06276 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1] K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] K07207 tuberous sclerosis 2 K07206 tuberous sclerosis 1 K07208 Ras homolog enriched in brain K07203 serine/threonine-protein kinase mTOR [EC:2.7.11.1] K07204 regulatory associated protein of mTOR K16184 proline-rich AKT1 substrate 1 K04688 ribosomal protein S6 kinase beta [EC:2.7.11.1] K07205 eukaryotic translation initiation factor 4E binding protein 1 K08530 peroxisome proliferator-activated receptor gamma K21357 serine/threonine-protein kinase ULK1 [EC:2.7.11.1] COMPOUND C00003 NAD+ C00008 ADP C00020 AMP C00022 Pyruvate C00024 Acetyl-CoA C00031 D-Glucose C00040 Acyl-CoA C00076 Calcium cation C00083 Malonyl-CoA C00085 D-Fructose 6-phosphate C00162 Fatty acid C00354 D-Fructose 1,6-bisphosphate C00389 Quercetin C00665 beta-D-Fructose 2,6-bisphosphate C00668 alpha-D-Glucose 6-phosphate C00698 Cl- C00757 Berberine C01172 beta-D-Glucose 6-phosphate C04677 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide C05981 Phosphatidylinositol-3,4,5-trisphosphate C07151 Metformin C09731 Epigallocatechin gallate D08351 Phenformin (BAN) REFERENCE PMID:19584320 AUTHORS Steinberg GR, Kemp BE TITLE AMPK in Health and Disease. JOURNAL Physiol Rev 89:1025-78 (2009) DOI:10.1152/physrev.00011.2008 REFERENCE PMID:15509864 AUTHORS Hardie DG. TITLE The AMP-activated protein kinase pathway--new players upstream and downstream. JOURNAL J Cell Sci 117:5479-87 (2004) DOI:10.1242/jcs.01540 REFERENCE PMID:23747347 AUTHORS Russo GL, Russo M, Ungaro P TITLE AMP-activated protein kinase: a target for old drugs against diabetes and cancer. JOURNAL Biochem Pharmacol 86:339-50 (2013) DOI:10.1016/j.bcp.2013.05.023 REFERENCE PMID:19393004 AUTHORS Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S TITLE AMPK in the brain: its roles in energy balance and neuroprotection. JOURNAL J Neurochem 109 Suppl 1:17-23 (2009) DOI:10.1111/j.1471-4159.2009.05916.x REFERENCE PMID:20010958 AUTHORS Li J, McCullough LD TITLE Effects of AMP-activated protein kinase in cerebral ischemia. JOURNAL J Cereb Blood Flow Metab 30:480-92 (2010) DOI:10.1038/jcbfm.2009.255 REFERENCE PMID:22700795 AUTHORS Sanchez AM, Candau RB, Csibi A, Pagano AF, Raibon A, Bernardi H TITLE The role of AMP-activated protein kinase in the coordination of skeletal muscle turnover and energy homeostasis. JOURNAL Am J Physiol Cell Physiol 303:C475-85 (2012) DOI:10.1152/ajpcell.00125.2012 REFERENCE PMID:16644802 AUTHORS Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, Hue L, Andreelli F TITLE Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. JOURNAL J Physiol 574:41-53 (2006) DOI:10.1113/jphysiol.2006.108506 REFERENCE PMID:19629071 AUTHORS Shackelford DB, Shaw RJ TITLE The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. JOURNAL Nat Rev Cancer 9:563-75 (2009) DOI:10.1038/nrc2676 REFERENCE PMID:22885100 AUTHORS Chung JH, Manganiello V, Dyck JR TITLE Resveratrol as a calorie restriction mimetic: therapeutic implications. JOURNAL Trends Cell Biol 22:546-54 (2012) DOI:10.1016/j.tcb.2012.07.004 REFERENCE PMID:20357764 AUTHORS Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, Ogata H, Kubota N, Takamoto I, Hayashi YK, Yamauchi N, Waki H, Fukayama M, Nishino I, Tokuyama K, Ueki K, Oike Y, Ishii S, Hirose K, Shimizu T, Touhara K, Kadowaki T TITLE Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. JOURNAL Nature 464:1313-9 (2010) DOI:10.1038/nature08991 REFERENCE PMID:17307971 AUTHORS Towler MC, Hardie DG TITLE AMP-activated protein kinase in metabolic control and insulin signaling. JOURNAL Circ Res 100:328-41 (2007) DOI:10.1161/01.RES.0000256090.42690.05 REFERENCE PMID:23899560 AUTHORS Richter EA, Hargreaves M TITLE Exercise, GLUT4, and skeletal muscle glucose uptake. JOURNAL Physiol Rev 93:993-1017 (2013) DOI:10.1152/physrev.00038.2012 REFERENCE PMID:16054041 AUTHORS Kahn BB, Alquier T, Carling D, Hardie DG TITLE AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. JOURNAL Cell Metab 1:15-25 (2005) DOI:10.1016/j.cmet.2004.12.003 REFERENCE PMID:23565491 AUTHORS Minokoshi Y, Toda C, Okamoto S TITLE Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle. JOURNAL Indian J Endocrinol Metab 16:S562-8 (2012) DOI:10.4103/2230-8210.105573 REFERENCE PMID:16723978 AUTHORS Guggino WB, Stanton BA TITLE New insights into cystic fibrosis: molecular switches that regulate CFTR. JOURNAL Nat Rev Mol Cell Biol 7:426-36 (2006) DOI:10.1038/nrm1949 REFERENCE PMID:16479585 AUTHORS Cheng A, Saltiel AR TITLE More TORC for the gluconeogenic engine. JOURNAL Bioessays 28:231-4 (2006) DOI:10.1002/bies.20375 REFERENCE PMID:19197243 AUTHORS Herrero-Martin G, Hoyer-Hansen M, Garcia-Garcia C, Fumarola C, Farkas T, Lopez-Rivas A, Jaattela M TITLE TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. JOURNAL EMBO J 28:677-85 (2009) DOI:10.1038/emboj.2009.8 REFERENCE PMID:19724019 AUTHORS Morris DL, Rui L TITLE Recent advances in understanding leptin signaling and leptin resistance. JOURNAL Am J Physiol Endocrinol Metab 297:E1247-59 (2009) DOI:10.1152/ajpendo.00274.2009 REFERENCE PMID:18725075 AUTHORS Minokoshi Y, Shiuchi T, Lee S, Suzuki A, Okamoto S TITLE Role of hypothalamic AMP-kinase in food intake regulation. JOURNAL Nutrition 24:786-90 (2008) DOI:10.1016/j.nut.2008.06.002 REFERENCE PMID:23024365 AUTHORS Miyamoto L, Ebihara K, Kusakabe T, Aotani D, Yamamoto-Kataoka S, Sakai T, Aizawa-Abe M, Yamamoto Y, Fujikura J, Hayashi T, Hosoda K, Nakao K TITLE Leptin activates hepatic 5'-AMP-activated protein kinase through sympathetic nervous system and alpha1-adrenergic receptor: a potential mechanism for improvement of fatty liver in lipodystrophy by leptin. JOURNAL J Biol Chem 287:40441-7 (2012) DOI:10.1074/jbc.M112.384545 REL_PATHWAY ko00010 Glycolysis / Gluconeogenesis ko00061 Fatty acid biosynthesis ko00500 Starch and sucrose metabolism ko01040 Biosynthesis of unsaturated fatty acids ko04110 Cell cycle ko04140 Autophagy - animal ko04150 mTOR signaling pathway ko04151 PI3K-Akt signaling pathway ko04910 Insulin signaling pathway ko04920 Adipocytokine signaling pathway ///