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 K00021 HMGCR; hydroxymethylglutaryl-CoA reductase (NADPH) [EC:1.1.1.34] K00507 SCD, desC; stearoyl-CoA desaturase (Delta-9 desaturase) [EC:1.14.19.1] K00665 FASN; fatty acid synthase, animal type [EC:2.3.1.85] K00693 GYS; glycogen synthase [EC:2.4.1.11] K00850 pfkA, PFK; 6-phosphofructokinase 1 [EC:2.7.1.11] K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] K01084 G6PC; glucose-6-phosphatase [EC:3.1.3.9] K01103 PFKFB3; 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 3 [EC:2.7.1.105 3.1.3.46] K01578 MLYCD; malonyl-CoA decarboxylase [EC:4.1.1.9] K01596 E4.1.1.32, pckA, PCK; phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32] K01946 ACACB; acetyl-CoA carboxylase / biotin carboxylase 2 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta K03234 EEF2; elongation factor 2 K03456 PPP2R1; serine/threonine-protein phosphatase 2A regulatory subunit A K03841 FBP; fructose-1,6-bisphosphatase I [EC:3.1.3.11] K04135 ADRA1A; adrenergic receptor alpha-1A K04354 PPP2R2; serine/threonine-protein phosphatase 2A regulatory subunit B K04382 PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16] K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25] K04456 AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1] K04503 CCND1; G1/S-specific cyclin-D1 K04526 INS; insulin K04527 INSR, CD220; insulin receptor [EC:2.7.10.1] K04688 RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1] K05031 CFTR, ABCC7; cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6] K05062 LEPR, CD295; leptin receptor K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1] K05424 LEP; leptin K05459 IGF1; insulin-like growth factor 1 K05870 CREB1; cyclic AMP-responsive element-binding protein 1 K06259 CD36; CD36 antigen K06276 PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1] K06627 CCNA; cyclin-A K07187 IRS2; insulin receptor substrate 2 K07188 LIPE, HSL; hormone-sensitive lipase [EC:3.1.1.79] K07191 SLC2A4, GLUT4; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 4 K07197 SREBP1, SREBF1; sterol regulatory element-binding transcription factor 1 K07198 PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K07199 PRKAB; 5'-AMP-activated protein kinase, regulatory beta subunit K07200 PRKAG; 5'-AMP-activated protein kinase, regulatory gamma subunit K07201 FOXO1; forkhead box protein O1 K07202 PPARGC1A, PGC1A; alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1] K07204 RAPTOR; regulatory associated protein of mTOR K07205 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 K07206 TSC1; tuberous sclerosis 1 K07207 TSC2; tuberous sclerosis 2 K07208 RHEB; Ras homolog enriched in brain K07292 NR2A1, HNF4A; hepatocyte nuclear factor 4-alpha K07296 ADIPOQ, ACDC; adiponectin K07297 ADIPOR; adiponectin receptor K07298 STK11, LKB1; serine/threonine-protein kinase 11 [EC:2.7.11.1] K07359 CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 [EC:2.7.11.17] K07877 RAB2A; Ras-related protein Rab-2A K07881 RAB14; Ras-related protein Rab-14 K07901 RAB8A, MEL; Ras-related protein Rab-8A K07903 RAB10; Ras-related protein Rab-10 K07905 RAB11B; Ras-related protein Rab-11B K08271 STRADA, LYK5; STE20-related kinase adapter protein alpha K08272 CAB39, MO25; calcium binding protein 39 K08292 EEF2K; elongation factor 2 kinase [EC:2.7.11.20] K08530 NR1C3, PPARG; peroxisome proliferator-activated receptor gamma K08765 CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21] K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5 K09048 CREB3; cyclic AMP-responsive element-binding protein 3 K09408 FOXO3; forkhead box protein O3 K11262 ACACA; acetyl-CoA carboxylase / biotin carboxylase 1 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K11411 SIRT1, SIR2L1; NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286] K11583 PPP2R3; serine/threonine-protein phosphatase 2A regulatory subunit B'' K11584 PPP2R5; serine/threonine-protein phosphatase 2A regulatory subunit B' K13088 ELAVL1, HUR; ELAV-like protein 1 K16172 IRS1; insulin receptor substrate 1 K16184 AKT1S1, PRAS40; proline-rich AKT1 substrate 1 K16333 CRTC2, TORC2; CREB-regulated transcription coactivator 2 K17445 IRS3; insulin receptor substrate 3 K17446 IRS4; insulin receptor substrate 4 K17532 STRADB; STE20-related kinase adapter protein beta K18341 TBC1D1; TBC1 domain family member 1 K19028 PFKFB1; 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 1 [EC:2.7.1.105 3.1.3.46] K19029 PFKFB2; 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2 [EC:2.7.1.105 3.1.3.46] K19030 PFKFB4; 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 4 [EC:2.7.1.105 3.1.3.46] K19523 CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21] K19524 CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21] K21357 ULK1; serine/threonine-protein kinase ULK1 [EC:2.7.11.1] K25893 CIDEA; cell death activator CIDE-A 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 ///