KEGG PATHWAY: ko04152

PATHWAY: ko04152

Entry

ko04152                     Pathway

Name

AMPK signaling pathway

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

ko04152

AMPK signaling pathway

Other DBs

GO:

2000479

Orthology

K04427

mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]

K07298

serine/threonine-protein kinase 11 [EC:2.7.11.1]

K08272

calcium binding protein 39

K08271

STE20-related kinase adapter protein alpha

K17532

STE20-related kinase adapter protein beta

K05424

leptin

K05062

leptin receptor

K07359

calcium/calmodulin-dependent protein kinase kinase 2 [EC:2.7.11.17]

K04135

adrenergic receptor alpha-1A

K07296

adiponectin

K07297

adiponectin receptor

K07198

5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31]

K07199

5'-AMP-activated protein kinase, regulatory beta subunit

K07200

5'-AMP-activated protein kinase, regulatory gamma subunit

K19028

6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 1 [EC:2.7.1.105 3.1.3.46]

K19029

6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2 [EC:2.7.1.105 3.1.3.46]

K01103

6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 3 [EC:2.7.1.105 3.1.3.46]

K19030

6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 4 [EC:2.7.1.105 3.1.3.46]

K03841

fructose-1,6-bisphosphatase I [EC:3.1.3.11]

K00850

6-phosphofructokinase 1 [EC:2.7.1.11]

K07292

hepatocyte nuclear factor 4-alpha

K01084

glucose-6-phosphatase [EC:3.1.3.9]

K01596

phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32]

K16333

CREB-regulated transcription coactivator 2

K05870

cyclic AMP-responsive element-binding protein 1

K09048

cyclic AMP-responsive element-binding protein 3

K09047

cyclic AMP-responsive element-binding protein 5

K07202

alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha

K13088

ELAV-like protein 1

K04503

G1/S-specific cyclin-D1

K06627

cyclin-A

K08292

elongation factor 2 kinase [EC:2.7.11.20]

K03234

elongation factor 2

K07201

forkhead box protein O1

K09408

forkhead box protein O3

K11411

NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286]

K07191

MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 4

K00693

glycogen synthase [EC:2.4.1.11]

K07188

hormone-sensitive lipase [EC:3.1.1.79]

K00021

hydroxymethylglutaryl-CoA reductase (NADPH) [EC:1.1.1.34]

K07197

sterol regulatory element-binding transcription factor 1

K00665

fatty acid synthase, animal type [EC:2.3.1.85]

K11262

acetyl-CoA carboxylase / biotin carboxylase 1 [EC:6.4.1.2 6.3.4.14 2.1.3.15]

K00507

stearoyl-CoA desaturase (Delta-9 desaturase) [EC:1.14.19.1]

K01946

acetyl-CoA carboxylase / biotin carboxylase 2 [EC:6.4.1.2 6.3.4.14 2.1.3.15]

K01578

malonyl-CoA decarboxylase [EC:4.1.1.9]

K08765

carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21]

K19523

carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21]

K19524

carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21]

K25893

cell death activator CIDE-A

K04382

serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]

K03456

serine/threonine-protein phosphatase 2A regulatory subunit A

K04354

serine/threonine-protein phosphatase 2A regulatory subunit B

K11583

serine/threonine-protein phosphatase 2A regulatory subunit B''

K11584

serine/threonine-protein phosphatase 2A regulatory subunit B'

K18341

TBC1 domain family member 1

K07877

Ras-related protein Rab-2A

K07901

Ras-related protein Rab-8A

K07903

Ras-related protein Rab-10

K07905

Ras-related protein Rab-11B

K07881

Ras-related protein Rab-14

K05031

cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6]

K06259

CD36 antigen

K05459

insulin-like growth factor 1

K05087

insulin-like growth factor 1 receptor [EC:2.7.10.1]

K04526

insulin

K04527

insulin receptor [EC:2.7.10.1]

K16172

insulin receptor substrate 1

K07187

insulin receptor substrate 2

K17445

insulin receptor substrate 3

K17446

insulin receptor substrate 4

K00922

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K02649

phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K06276

3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]

K04456

RAC serine/threonine-protein kinase [EC:2.7.11.1]

K07207

tuberous sclerosis 2

K07206

tuberous sclerosis 1

K07208

Ras homolog enriched in brain

K07203

serine/threonine-protein kinase mTOR [EC:2.7.11.1]

K07204

regulatory associated protein of mTOR

K16184

proline-rich AKT1 substrate 1

K04688

ribosomal protein S6 kinase beta [EC:2.7.11.1]

K07205

eukaryotic translation initiation factor 4E binding protein 1

K08530

peroxisome proliferator-activated receptor gamma

K21357

serine/threonine-protein kinase ULK1 [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

ko00010

Glycolysis / Gluconeogenesis

ko00061

Fatty acid biosynthesis

ko00500

Starch and sucrose metabolism

ko01040

Biosynthesis of unsaturated fatty acids

ko04110