KEGG   PATHWAY: setr04152
Entry
setr04152                   Pathway                                
Name
AMPK signaling pathway - Suncus etruscus (white-toothed pygmy shrew)
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
setr04152  AMPK signaling pathway
setr04152

Other DBs
GO: 2000479
Organism
Suncus etruscus (white-toothed pygmy shrew) [GN:setr]
Gene
126006708  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
126029629  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
126002082  CAB39; calcium-binding protein 39 [KO:K08272]
126016260  CAB39L; calcium-binding protein 39-like [KO:K08272]
126017900  STRADA; STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
126009010  STRADB; STE20-related kinase adapter protein beta [KO:K17532]
126011924  LEP; leptin [KO:K05424]
126011639  LEPR; leptin receptor [KO:K05062]
126030591  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
126003304  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
126011986  ADIPOQ; adiponectin [KO:K07296]
126004198  ADIPOR1; adiponectin receptor protein 1 [KO:K07297]
126022342  ADIPOR2; adiponectin receptor protein 2 [KO:K07297]
126007266  LOW QUALITY PROTEIN: adiponectin receptor protein 1-like [KO:K07297]
125999227  adiponectin receptor protein 1-like [KO:K07297]
126000044  PRKAA1; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
126010983  PRKAA2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
126020754  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
126030640  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
126022562  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
126014825  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
126001663  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
126003558  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
126013286  PFKFB3; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 isoform X1 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
126014057  PFKFB4; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 4 [KO:K19030] [EC:2.7.1.105 3.1.3.46]
126006752  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
126006801  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
126013282  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
126022330  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
126025629  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
126017352  HNF4A; hepatocyte nuclear factor 4-alpha isoform X1 [KO:K07292]
126009115  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
126000890  G6PC1; LOW QUALITY PROTEIN: glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
126018615  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
126001919  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
126013306  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
126020792  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
126008959  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
126029685  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
126012179  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
126009210  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
126017927  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
126020129  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
126020515  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
126032337  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
126031159  ELAVL1; ELAV-like protein 1 [KO:K13088]
126019074  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
126004459  CCNA2; cyclin-A2 [KO:K06627]
126016279  CCNA1; cyclin-A1 [KO:K06627]
126031218  EEF2K; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
126029658  EEF2; elongation factor 2 [KO:K03234]
126016208  FOXO1; forkhead box protein O1 [KO:K07201]
126005875  FOXO3; forkhead box protein O3 [KO:K09408]
125995006  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
125997945  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
126022855  GYS2; LOW QUALITY PROTEIN: glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
126027190  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
126028546  LIPE; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
126001477  HMGCR; 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [KO:K00021] [EC:1.1.1.34]
126013653  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
126013899  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
126007770  ACACA; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125994780  SCD; stearoyl-CoA desaturase [KO:K00507] [EC:1.14.19.1]
126032644  SCD5; stearoyl-CoA desaturase 5 [KO:K00507] [EC:1.14.19.1]
126031109  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
126027240  MLYCD; malonyl-CoA decarboxylase, mitochondrial isoform X1 [KO:K01578] [EC:4.1.1.9]
126019050  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
126006359  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
126027189  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
126003793  CIDEA; cell death activator CIDE-A [KO:K25893]
126006854  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
126027762  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
126016114  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
126027984  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
126003303  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
126020954  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
126006109  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
126033612  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
126012121  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
125998609  PPP2R3C; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
126000642  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
126003555  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
126003563  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
126004025  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
125995970  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
125997295  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform-like [KO:K11584]
126018881  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
126032428  TBC1D1; TBC1 domain family member 1 [KO:K18341]
126020486  RAB2A; ras-related protein Rab-2A isoform X1 [KO:K07877]
126031096  ras-related protein Rab-2A [KO:K07877]
126029472  RAB8A; ras-related protein Rab-8A [KO:K07901]
126024054  RAB10; ras-related protein Rab-10 [KO:K07903]
126031180  RAB11B; ras-related protein Rab-11B [KO:K07905]
126008805  RAB14; ras-related protein Rab-14 [KO:K07881]
126016360  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
126022453  platelet glycoprotein 4 [KO:K06259]
126022459  platelet glycoprotein 4-like [KO:K06259]
126022310  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
126021814  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
126019098  INS; insulin [KO:K04526]
126031127  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
126001122  IRS1; insulin receptor substrate 1 [KO:K16172]
126015552  IRS2; insulin receptor substrate 2 [KO:K07187]
126029954  insulin receptor substrate 1-like [KO:K17445]
125999066  IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
126012035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
126012036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
126011501  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
126030200  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
126011086  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
126001552  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
126001240  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
126013417  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
126033346  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126028133  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126000897  TSC2; tuberin isoform X1 [KO:K07207]
126009519  TSC1; hamartin [KO:K07206]
126016192  RHEB; GTP-binding protein Rheb [KO:K07208]
126011494  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
126012995  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
126027823  AKT1S1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
126006378  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
126019034  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
126006470  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
125998082  PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530]
126001085  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
setr00010  Glycolysis / Gluconeogenesis
setr00061  Fatty acid biosynthesis
setr00500  Starch and sucrose metabolism
setr01040  Biosynthesis of unsaturated fatty acids
setr04110  Cell cycle
setr04140  Autophagy - animal
setr04150  mTOR signaling pathway
setr04151  PI3K-Akt signaling pathway
setr04910  Insulin signaling pathway
setr04920  Adipocytokine signaling pathway
KO pathway
ko04152   
LinkDB

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