KEGG   PATHWAY: ncar04152
Entry
ncar04152                   Pathway                                
Name
AMPK signaling pathway - Sciurus carolinensis (gray squirrel)
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
ncar04152  AMPK signaling pathway
ncar04152

Other DBs
GO: 2000479
Organism
Sciurus carolinensis (gray squirrel) [GN:ncar]
Gene
124988810  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
124968687  serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
124984586  calcium-binding protein 39-like [KO:K08272]
124979211  calcium-binding protein 39 [KO:K08272]
124980232  STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
124979106  STE20-related kinase adapter protein beta [KO:K17532]
124991634  leptin [KO:K05424]
124960271  leptin receptor-like isoform X1 [KO:K05062]
124990307  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1 [KO:K07359] [EC:2.7.11.17]
124982077  alpha-1A adrenergic receptor isoform X1 [KO:K04135]
124992968  adiponectin [KO:K07296]
124962190  adiponectin receptor protein 1 [KO:K07297]
124981003  adiponectin receptor protein 1-like [KO:K07297]
124982885  adiponectin receptor protein 2 [KO:K07297]
124976120  LOW QUALITY PROTEIN: adiponectin receptor protein 1-like [KO:K07297]
124987007  5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
124983683  5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
124990233  5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
124960770  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
124990239  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
124980693  5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
124983681  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
124971391  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
124961597  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
124961497  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 isoform X1 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
124993097  LOW QUALITY PROTEIN: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4-like [KO:K19030] [EC:2.7.1.105 3.1.3.46]
124965552  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
124965839  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
124992452  ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
124961595  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
124981973  ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
124977858  hepatocyte nuclear factor 4-alpha isoform X1 [KO:K07292]
124979177  glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
124980360  glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
124981415  glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
124978312  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
124970845  phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
124964238  CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
124979032  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
124991113  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
124958938  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
124984689  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
124969564  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
124964377  cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048]
124991182  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
124994408  peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
124968336  ELAV-like protein 1 [KO:K13088]
124958520  G1/S-specific cyclin-D1 [KO:K04503]
124994687  LOW QUALITY PROTEIN: cyclin-A2-like [KO:K06627]
124985165  cyclin-A1 [KO:K06627]
124970151  eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
124968834  elongation factor 2 [KO:K03234]
124985154  forkhead box protein O1 [KO:K07201]
124989730  forkhead box protein O3 [KO:K09408]
124985129  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
124980544  solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
124982028  glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
124966164  LOW QUALITY PROTEIN: glycogen [starch] synthase, muscle-like [KO:K00693] [EC:2.4.1.11]
124966648  hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
124987348  3-hydroxy-3-methylglutaryl-coenzyme A reductase [KO:K00021] [EC:1.1.1.34]
124980543  sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
124979686  fatty acid synthase-like isoform X1 [KO:K00665] [EC:2.3.1.85]
124980304  acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
124994604  stearoyl-CoA desaturase 5 [KO:K00507] [EC:1.14.19.1]
124984655  acyl-CoA desaturase 1 [KO:K00507] [EC:1.14.19.1]
124984908  acyl-CoA desaturase 3-like [KO:K00507] [EC:1.14.19.1]
124985066  acyl-CoA desaturase 1-like [KO:K00507] [EC:1.14.19.1]
124985309  acyl-CoA desaturase 1-like [KO:K00507] [EC:1.14.19.1]
124990202  acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
124967129  malonyl-CoA decarboxylase, mitochondrial [KO:K01578] [EC:4.1.1.9]
124958962  carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
124983218  carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
124967617  carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
124965230  cell death activator CIDE-A isoform X1 [KO:K25893]
124987135  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
124983945  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
124958287  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
124967003  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
124986762  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
124994837  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform isoform X1 [KO:K04354]
124984746  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
124982397  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
124993238  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
124977718  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
124962449  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma-like [KO:K11583]
124975681  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
124958310  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
124988657  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
124976854  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
124961576  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
124973978  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform-like [KO:K11584]
124976126  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
124994430  TBC1 domain family member 1 isoform X1 [KO:K18341]
124983413  ras-related protein Rab-2A [KO:K07877]
124985792  LOW QUALITY PROTEIN: ras-related protein Rab-8A-like [KO:K07901]
124969448  ras-related protein Rab-8A [KO:K07901]
124962769  ras-related protein Rab-10 [KO:K07903]
124968499  ras-related protein Rab-11B [KO:K07905]
124964388  ras-related protein Rab-14 isoform X1 [KO:K07881]
124991796  cystic fibrosis transmembrane conductance regulator isoform X1 [KO:K05031] [EC:5.6.1.6]
124990830  platelet glycoprotein 4 [KO:K06259]
124983128  insulin-like growth factor I isoform X1 [KO:K05459]
124978062  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
124960685  insulin [KO:K04526]
124968393  insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
124979751  insulin receptor substrate 1 [KO:K16172]
124984569  insulin receptor substrate 2 [KO:K07187]
124970787  insulin receptor substrate 1-like [KO:K17445]
124972126  insulin receptor substrate 4 [KO:K17446]
124993166  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124993330  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124963509  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
124986648  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124968815  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124970168  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
124962260  LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
124976076  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124966582  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124970035  tuberin isoform X1 [KO:K07207]
124964393  hamartin isoform X1 [KO:K07206]
124990711  GTP-binding protein Rheb [KO:K07208]
124979992  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
124979635  LOW QUALITY PROTEIN: regulatory-associated protein of mTOR-like [KO:K07204]
124967127  proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
124958805  ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
124978930  ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
124991326  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
124983324  eukaryotic translation initiation factor 4E-binding protein 1 isoform X1 [KO:K07205]
124971234  peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
124990355  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
ncar00010  Glycolysis / Gluconeogenesis
ncar00061  Fatty acid biosynthesis
ncar00500  Starch and sucrose metabolism
ncar01040  Biosynthesis of unsaturated fatty acids
ncar04110  Cell cycle
ncar04140  Autophagy - animal
ncar04150  mTOR signaling pathway
ncar04151  PI3K-Akt signaling pathway
ncar04910  Insulin signaling pathway
ncar04920  Adipocytokine signaling pathway
KO pathway
ko04152   
LinkDB

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