KEGG   PATHWAY: tod04152
Entry
tod04152                    Pathway                                
Name
AMPK signaling pathway - Talpa occidentalis (Iberian mole)
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
tod04152  AMPK signaling pathway
tod04152

Other DBs
GO: 2000479
Organism
Talpa occidentalis (Iberian mole) [GN:tod]
Gene
119252700  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
119240488  STK11; serine/threonine-protein kinase STK11 isoform X2 [KO:K07298] [EC:2.7.11.1]
119258900  CAB39L; calcium-binding protein 39-like [KO:K08272]
119256285  CAB39; calcium-binding protein 39 [KO:K08272]
119232634  STRADA; STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
119256104  STRADB; STE20-related kinase adapter protein beta [KO:K17532]
119252583  LEP; leptin [KO:K05424]
119237045  LEPR; leptin receptor isoform X1 [KO:K05062]
119245010  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 isoform X1 [KO:K07359] [EC:2.7.11.17]
119233905  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
119257381  ADIPOQ; adiponectin [KO:K07296]
119234442  ADIPOR1; adiponectin receptor protein 1 isoform X1 [KO:K07297]
119247850  ADIPOR2; adiponectin receptor protein 2 [KO:K07297]
119235081  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
119260486  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
119235510  PRKAB2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
119244924  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
119247883  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
119256218  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
119249017  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X5 [KO:K07200]
119246700  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
119233431  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
119244659  PFKFB3; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 isoform X2 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
119259604  PFKFB4; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 4 isoform X1 [KO:K19030] [EC:2.7.1.105 3.1.3.46]
119230686  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
119231981  FBP2; fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
119244646  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X2 [KO:K00850] [EC:2.7.1.11]
119247590  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
119257153  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
119235647  HNF4A; hepatocyte nuclear factor 4-alpha isoform X1 [KO:K07292]
119230428  G6PC1; glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
119230539  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
119254775  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
119238940  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
119254664  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
119236119  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
119256146  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
119232783  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
119235594  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
119246923  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
119239846  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
119247555  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
119255317  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
119243789  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X3 [KO:K09047]
119260209  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X2 [KO:K07202]
119240441  ELAVL1; ELAV-like protein 1 isoform X1 [KO:K13088]
119249876  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
119246910  LOW QUALITY PROTEIN: G1/S-specific cyclin-D1-like [KO:K04503]
119234789  CCNA2; cyclin-A2 [KO:K06627]
119258844  CCNA1; cyclin-A1 [KO:K06627]
119241842  EEF2K; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
119240574  EEF2; elongation factor 2 [KO:K03234]
119258862  FOXO1; forkhead box protein O1 [KO:K07201]
119252757  FOXO3; forkhead box protein O3 isoform X1 [KO:K09408]
119233504  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
119232046  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
119248315  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
119249557  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
119249387  LIPE; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
119260566  HMGCR; 3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1 [KO:K00021] [EC:1.1.1.34]
119230754  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
119231088  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
119232875  ACACA; acetyl-CoA carboxylase 1 isoform X3 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119233897  SCD; stearoyl-CoA desaturase [KO:K00507] [EC:1.14.19.1]
119261327  SCD5; stearoyl-CoA desaturase 5 [KO:K00507] [EC:1.14.19.1]
119244882  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119249135  MLYCD; malonyl-CoA decarboxylase, mitochondrial [KO:K01578] [EC:4.1.1.9]
119249881  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
119247127  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
119249597  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
119243206  CIDEA; cell death activator CIDE-A isoform X1 [KO:K25893]
119257786  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
119243468  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
119249625  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
119240660  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
119234435  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
119242887  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X4 [KO:K04354]
119260982  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
119257744  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
119239016  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
119246800  PPP2R3B; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
119234468  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
119250005  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
119252478  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
119239170  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
119239382  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
119260620  TBC1D1; TBC1 domain family member 1 isoform X1 [KO:K18341]
119241170  RAB2A; ras-related protein Rab-2A [KO:K07877]
119241068  RAB8A; ras-related protein Rab-8A isoform X1 [KO:K07901]
119258673  RAB10; ras-related protein Rab-10 [KO:K07903]
119240452  RAB11B; ras-related protein Rab-11B [KO:K07905]
119230523  RAB14; ras-related protein Rab-14 isoform X1 [KO:K07881]
119250439  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
119244841  CD36; platelet glycoprotein 4 [KO:K06259]
119247369  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
119245137  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
119249861  INS; LOW QUALITY PROTEIN: insulin [KO:K04526]
119240421  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
119256266  IRS1; insulin receptor substrate 1 [KO:K16172]
119259653  IRS2; LOW QUALITY PROTEIN: insulin receptor substrate 2 [KO:K07187]
119242334  insulin receptor substrate 1-like [KO:K17445]
119245973  IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
119257726  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119236721  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
119257304  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119237093  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119260810  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119241117  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119242012  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
119244519  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
119239481  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119249321  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119242027  TSC2; tuberin isoform X1 [KO:K07207]
119231219  TSC1; hamartin [KO:K07206]
119249007  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
119235686  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
119232762  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
119249606  AKT1S1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
119232527  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119249909  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
119257810  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
119255673  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
119245083  ULK1; serine/threonine-protein kinase ULK1 isoform X2 [KO:K21357] [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
Related
pathway
tod00010  Glycolysis / Gluconeogenesis
tod00061  Fatty acid biosynthesis
tod00500  Starch and sucrose metabolism
tod01040  Biosynthesis of unsaturated fatty acids
tod04110  Cell cycle
tod04140  Autophagy - animal
tod04150  mTOR signaling pathway
tod04151  PI3K-Akt signaling pathway
tod04910  Insulin signaling pathway
tod04920  Adipocytokine signaling pathway
KO pathway
ko04152   
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