KEGG   PATHWAY: rno04152
Entry
rno04152                    Pathway                                
Name
AMPK signaling pathway - Rattus norvegicus (rat)
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
rno04152  AMPK signaling pathway
rno04152

Other DBs
GO: 2000479
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
313121  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
314621  Stk11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
301574  Cab39; calcium-binding protein 39 isoform 1 [KO:K08272]
290291  Cab39l; calcium-binding protein 39-like [KO:K08272]
303605  Strada; STE20-related kinase adapter protein alpha isoform 2 [KO:K08271]
501146  Stradb; STE20-related kinase adapter protein beta [KO:K17532]
25608  Lep; leptin precursor [KO:K05424]
24536  Lepr; leptin receptor precursor [KO:K05062]
83506  Camkk2; calcium/calmodulin-dependent protein kinase kinase 2 isoform 1 [KO:K07359] [EC:2.7.11.17]
29412  Adra1a; alpha-1A adrenergic receptor [KO:K04135]
246253  Adipoq; adiponectin precursor [KO:K07296]
312670  Adipor2; adiponectin receptor protein 2 [KO:K07297]
289036  Adipor1; adiponectin receptor protein 1 [KO:K07297]
65248  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
78975  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
83803  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
64562  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
25520  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
301518  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
24638  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
24640  Pfkfb2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform a [KO:K19029] [EC:2.7.1.105 3.1.3.46]
117276  Pfkfb3; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 [KO:K01103] [EC:2.7.1.105 3.1.3.46]
54283  Pfkfb4; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 4 [KO:K19030] [EC:2.7.1.105 3.1.3.46]
24362  Fbp1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
114508  Fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
65152  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
25741  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
60416  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
25735  Hnf4a; hepatocyte nuclear factor 4-alpha isoform 1 [KO:K07292]
25634  G6pc1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
303565  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
362282  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
361042  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
310615  Crtc2; CREB-regulated transcription coactivator 2 [KO:K16333]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
310616  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
362165  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
362339  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
314638  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
500131  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
83516  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
363854  Elavl1; ELAV-like protein 1 [KO:K13088]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
114494  Ccna2; cyclin-A2 [KO:K06627]
295052  Ccna1; cyclin-A1 [KO:K06627]
25435  Eef2k; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
29565  Eef2; elongation factor 2 [KO:K03234]
84482  Foxo1; forkhead box protein O1 [KO:K07201]
294515  Foxo3; forkhead box protein O3 [KO:K09408]
309757  Sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
25139  Slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
25623  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
690987  Gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
25330  Lipe; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
25675  Hmgcr; 3-hydroxy-3-methylglutaryl-coenzyme A reductase [KO:K00021] [EC:1.1.1.34]
78968  Srebf1; sterol regulatory element-binding protein 1 isoform 1 precursor [KO:K07197]
50671  Fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
60581  Acaca; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
83792  Scd2; stearoyl-CoA desaturase 2 [KO:K00507] [EC:1.14.19.1]
246074  Scd; acyl-CoA desaturase 1 [KO:K00507] [EC:1.14.19.1]
499358  Scd4; stearoyl-CoA desaturase 4 [KO:K00507] [EC:1.14.19.1]
681458  Scd3; acyl-CoA desaturase 3 [KO:K00507] [EC:1.14.19.1]
116719  Acacb; acetyl-CoA carboxylase 2 precursor [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
85239  Mlycd; malonyl-CoA decarboxylase, mitochondrial [KO:K01578] [EC:4.1.1.9]
25757  Cpt1a; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
25756  Cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
308579  Cpt1c; palmitoyl thioesterase CPT1C [KO:K19524] [EC:2.3.1.21]
291541  Cidea; lipid transferase CIDEA [KO:K25893]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100362453  Ppp2cal1; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
246255  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
60660  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform 1 [KO:K04354]
117256  Ppp2r2c; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform isoform 1 [KO:K04354]
117104  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
682033  Ppp2r3b; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
362739  Ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
363122  Ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
309179  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
691318  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform 4 [KO:K11584]
363193  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
299147  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
312754  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
360937  Tbc1d1; TBC1 domain family member 1 [KO:K18341]
65158  Rab2a; ras-related protein Rab-2A [KO:K07877]
117103  Rab8a; ras-related protein Rab-8A [KO:K07901]
50993  Rab10; ras-related protein Rab-10 [KO:K07903]
79434  Rab11b; ras-related protein Rab-11B [KO:K07905]
94197  Rab14; ras-related protein Rab-14 [KO:K07881]
24255  Cftr; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
29184  Cd36; platelet glycoprotein 4 [KO:K06259]
499985  Cd36l1; CD36 molecule like 1 [KO:K06259]
120093085  Cd36-ps1; platelet glycoprotein 4-like [KO:K06259]
134486712  platelet glycoprotein 4-like [KO:K06259]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
25718  Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087] [EC:2.7.10.1]
24506  Ins2; insulin-2 preproprotein [KO:K04526]
24505  Ins1; insulin-1 preproprotein [KO:K04526]
24954  Insr; insulin receptor preproprotein [KO:K04527] [EC:2.7.10.1]
25467  Irs1; insulin receptor substrate 1 [KO:K16172]
29376  Irs2; insulin receptor substrate 2 [KO:K07187]
84021  Irs3; insulin receptor substrate 3 [KO:K17445]
315350  Irs4; insulin receptor substrate 4 [KO:K17446]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24855  Tsc2; tuberin [KO:K07207]
60445  Tsc1; hamartin [KO:K07206]
26954  Rheb; GTP-binding protein Rheb [KO:K07208]
56718  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
287871  Rptor; regulatory-associated protein of mTOR [KO:K07204]
292887  Akt1s1; proline-rich AKT1 substrate 1 [KO:K16184]
83840  Rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
361696  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
116636  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
25664  Pparg; peroxisome proliferator-activated receptor gamma isoform 1 [KO:K08530]
360827  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
rno00010  Glycolysis / Gluconeogenesis
rno00061  Fatty acid biosynthesis
rno00500  Starch and sucrose metabolism
rno01040  Biosynthesis of unsaturated fatty acids
rno04110  Cell cycle
rno04140  Autophagy - animal
rno04150  mTOR signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04910  Insulin signaling pathway
rno04920  Adipocytokine signaling pathway
KO pathway
ko04152   
LinkDB

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