KEGG   PATHWAY: pale04152
Entry
pale04152                   Pathway                                
Name
AMPK signaling pathway - Pteropus alecto (black flying fox)
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
pale04152  AMPK signaling pathway
pale04152

Other DBs
GO: 2000479
Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102882452  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102880044  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
102887892  CAB39; calcium-binding protein 39 [KO:K08272]
102894759  CAB39L; calcium-binding protein 39-like [KO:K08272]
102878399  STRADA; STE20-related kinase adapter protein alpha isoform X4 [KO:K08271]
102878936  STRADB; STE20-related kinase adapter protein beta isoform X1 [KO:K17532]
102896937  LEP; leptin [KO:K05424]
102882664  LEPR; leptin receptor [KO:K05062]
102884660  CAMKK2; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
102884516  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
102886469  ADIPOQ; adiponectin [KO:K07296]
102881940  ADIPOR2; adiponectin receptor protein 2 isoform X1 [KO:K07297]
102882957  ADIPOR1; adiponectin receptor protein 1 [KO:K07297]
102884524  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
102886520  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
102886980  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
102887949  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
102898038  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
102882613  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X3 [KO:K07200]
102887347  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
102897563  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
102885287  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
102892155  PFKFB3; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
102888568  PFKFB4; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 4 [KO:K19030] [EC:2.7.1.105 3.1.3.46]
102882419  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
102882663  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
102894946  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
102886089  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X3 [KO:K00850] [EC:2.7.1.11]
102893676  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
102878260  HNF4A; hepatocyte nuclear factor 4-alpha isoform X1 [KO:K07292]
102887492  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
102896886  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
102898137  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
102888528  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
102897596  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
102879203  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
102888198  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102878515  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
102894633  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
102882888  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
102886510  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
102879289  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
102884583  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102879270  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
102891391  ELAVL1; ELAV-like protein 1 [KO:K13088]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102890664  CCNA1; cyclin-A1 [KO:K06627]
102894080  CCNA2; cyclin-A2 [KO:K06627]
102897678  EEF2K; eukaryotic elongation factor 2 kinase isoform X1 [KO:K08292] [EC:2.7.11.20]
102892962  EEF2; elongation factor 2 [KO:K03234]
102892244  FOXO1; forkhead box protein O1 [KO:K07201]
102890472  FOXO3; forkhead box protein O3 [KO:K09408]
102880351  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
102881931  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191]
102890809  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
102884634  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
102889858  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
102890076  HMGCR; 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [KO:K00021] [EC:1.1.1.34]
102882131  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
102887167  FASN; LOW QUALITY PROTEIN: fatty acid synthase [KO:K00665] [EC:2.3.1.85]
102895052  ACACA; acetyl-CoA carboxylase 1 isoform X3 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
102891827  SCD5; stearoyl-CoA desaturase 5 [KO:K00507] [EC:1.14.19.1]
102878466  SCD; acyl-CoA desaturase [KO:K00507] [EC:1.14.19.1]
102887451  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
102896503  MLYCD; malonyl-CoA decarboxylase, mitochondrial isoform X1 [KO:K01578] [EC:4.1.1.9]
102886073  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
102879520  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X2 [KO:K19523] [EC:2.3.1.21]
102878033  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
102881956  CIDEA; cell death activator CIDE-A [KO:K25893]
102885289  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102887013  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102894487  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
102888699  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102888692  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
102882824  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
102892945  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
102896806  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
102891533  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
102884648  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
102879054  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102897902  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
102895399  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
102881266  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102898938  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102895605  TBC1D1; TBC1 domain family member 1 isoform X1 [KO:K18341]
102884708  RAB2A; ras-related protein Rab-2A [KO:K07877]
102888123  RAB8A; ras-related protein Rab-8A [KO:K07901]
102889067  RAB10; ras-related protein Rab-10 [KO:K07903]
102889088  RAB11B; ras-related protein Rab-11B [KO:K07905]
102893098  RAB14; ras-related protein Rab-14 [KO:K07881]
102884577  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
102885145  CD36; platelet glycoprotein 4 [KO:K06259]
102890331  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
102885962  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102881117  insulin [KO:K04526]
102879346  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
102891583  IRS1; insulin receptor substrate 1 [KO:K16172]
102898575  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
102895007  IRS4; insulin receptor substrate 4 [KO:K17446]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102896950  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102898762  TSC2; tuberin isoform X11 [KO:K07207]
102878835  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
102889101  RHEB; GTP-binding protein Rheb [KO:K07208]
102885092  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102885334  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
102897877  AKT1S1; LOW QUALITY PROTEIN: proline-rich AKT1 substrate 1 [KO:K16184]
102891214  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102889369  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
102881655  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
102892450  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
102893241  ULK1; serine/threonine-protein kinase ULK1 [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
pale00010  Glycolysis / Gluconeogenesis
pale00061  Fatty acid biosynthesis
pale00500  Starch and sucrose metabolism
pale01040  Biosynthesis of unsaturated fatty acids
pale04110  Cell cycle
pale04140  Autophagy - animal
pale04150  mTOR signaling pathway
pale04151  PI3K-Akt signaling pathway
pale04910  Insulin signaling pathway
pale04920  Adipocytokine signaling pathway
KO pathway
ko04152   
LinkDB

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