KEGG   PATHWAY: nle04152
Entry
nle04152                    Pathway                                
Name
AMPK signaling pathway - Nomascus leucogenys (northern white-cheeked gibbon)
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
nle04152  AMPK signaling pathway
nle04152

Other DBs
GO: 2000479
Organism
Nomascus leucogenys (northern white-cheeked gibbon) [GN:nle]
Gene
100596471  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100602473  STK11; serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
100593463  CAB39L; calcium-binding protein 39-like isoform X1 [KO:K08272]
100586986  CAB39; calcium-binding protein 39 [KO:K08272]
100588298  STRADA; STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
100594976  STRADB; STE20-related kinase adapter protein beta [KO:K17532]
100590604  LEP; leptin isoform X1 [KO:K05424]
100602850  LEPR; leptin receptor isoform X3 [KO:K05062]
100590503  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 isoform X1 [KO:K07359] [EC:2.7.11.17]
100584192  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
100599297  ADIPOQ; adiponectin [KO:K07296]
100598273  ADIPOR2; adiponectin receptor protein 2 isoform X1 [KO:K07297]
100596078  ADIPOR1; adiponectin receptor protein 1 [KO:K07297]
100582042  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
100595096  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
100600676  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
100597131  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
100598921  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X3 [KO:K07200]
100607037  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
100606474  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
100606264  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
100585652  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
100582783  PFKFB3; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 isoform X1 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
100592158  PFKFB4; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 4 isoform X1 [KO:K19030] [EC:2.7.1.105 3.1.3.46]
100579897  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
100598420  FBP1; fructose-1,6-bisphosphatase 1 isoform X1 [KO:K03841] [EC:3.1.3.11]
115835451  fructose-1,6-bisphosphatase isozyme 2-like [KO:K03841] [EC:3.1.3.11]
100587636  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
100582114  ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
100601116  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
115833153  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
100593478  HNF4A; hepatocyte nuclear factor 4-alpha isoform X1 [KO:K07292]
100607569  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
100584622  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
100607735  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
100580806  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
100583855  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
100597840  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
100586647  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
100603387  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100595943  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100594080  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100597876  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100592170  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100600059  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100589460  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
100607927  ELAVL1; ELAV-like protein 1 isoform X1 [KO:K13088]
100605736  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100594705  CCNA1; cyclin-A1 isoform X3 [KO:K06627]
105740029  CCNA2; cyclin-A2 [KO:K06627]
100591954  EEF2K; eukaryotic elongation factor 2 kinase isoform X1 [KO:K08292] [EC:2.7.11.20]
100590476  EEF2; elongation factor 2 [KO:K03234]
100594615  FOXO1; forkhead box protein O1 [KO:K07201]
100600519  FOXO3; forkhead box protein O3 [KO:K09408]
100605499  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
100587831  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191]
100579728  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
101177222  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
100603864  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
100597442  HMGCR; 3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1 [KO:K00021] [EC:1.1.1.34]
100591724  SREBF1; sterol regulatory element-binding protein 1 isoform X3 [KO:K07197]
100597701  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
100596750  LOW QUALITY PROTEIN: fatty acid synthase-like [KO:K00665] [EC:2.3.1.85]
100588574  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100602453  SCD; acyl-CoA desaturase [KO:K00507] [EC:1.14.19.1]
100599363  SCD5; stearoyl-CoA desaturase 5 [KO:K00507] [EC:1.14.19.1]
100606756  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100590554  MLYCD; malonyl-CoA decarboxylase, mitochondrial [KO:K01578] [EC:4.1.1.9]
100588984  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
100591075  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
100601001  CIDEA; cell death activator CIDE-A isoform X2 [KO:K25893]
100596525  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100585393  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100605248  PPP2R1B; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
100598916  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100584267  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X2 [KO:K04354]
100585667  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
100583131  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X5 [KO:K04354]
100583311  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
100597427  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
100600043  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
115833850  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
100592661  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
100602668  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
100605694  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
100600164  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
100600883  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X4 [KO:K11584]
100601007  TBC1D1; TBC1 domain family member 1 isoform X3 [KO:K18341]
100580326  RAB2A; ras-related protein Rab-2A [KO:K07877]
100593627  RAB8A; ras-related protein Rab-8A [KO:K07901]
100592114  RAB10; ras-related protein Rab-10 [KO:K07903]
100580919  RAB11B; ras-related protein Rab-11B [KO:K07905]
100607466  RAB14; ras-related protein Rab-14 [KO:K07881]
100601480  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
100597566  CD36; platelet glycoprotein 4 [KO:K06259]
100595306  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
100593288  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
100586809  INS; insulin isoform X2 [KO:K04526]
100597533  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
100607873  IRS1; insulin receptor substrate 1 [KO:K16172]
100583956  IRS2; insulin receptor substrate 2 [KO:K07187]
100588594  IRS4; insulin receptor substrate 4 [KO:K17446]
100588218  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100580872  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100584384  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100605788  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100591270  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100599301  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100593010  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
115831277  LOW QUALITY PROTEIN: putative 3-phosphoinositide-dependent protein kinase 2 [KO:K06276] [EC:2.7.11.1]
100604331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100587864  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100587109  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100604902  tuberin isoform X1 [KO:K07207]
115831278  tuberin isoform X1 [KO:K07207]
100587112  TSC1; hamartin isoform X2 [KO:K07206]
100598486  RHEB; GTP-binding protein Rheb [KO:K07208]
100594291  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
100587259  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
100606336  AKT1S1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
100606492  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100593862  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105740136  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100581046  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
100583005  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [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
nle00010  Glycolysis / Gluconeogenesis
nle00061  Fatty acid biosynthesis
nle00500  Starch and sucrose metabolism
nle01040  Biosynthesis of unsaturated fatty acids
nle04110  Cell cycle
nle04140  Autophagy - animal
nle04150  mTOR signaling pathway
nle04151  PI3K-Akt signaling pathway
nle04910  Insulin signaling pathway
nle04920  Adipocytokine signaling pathway
KO pathway
ko04152   
LinkDB

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