Entry 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 transductionBRITE hierarchy
Pathway map Other DBs Orthology K00021 HMGCR; hydroxymethylglutaryl-CoA reductase (NADPH) [EC:1.1.1.34 ]
K00507 SCD, desC; stearoyl-CoA desaturase (Delta-9 desaturase) [EC:1.14.19.1 ]
K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01596 E4.1.1.32, pckA, PCK; phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32 ]
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03234 EEF2; elongation factor 2
K03456 PPP2R1; serine/threonine-protein phosphatase 2A regulatory subunit A
K04135 ADRA1A; adrenergic receptor alpha-1A
K04354 PPP2R2; serine/threonine-protein phosphatase 2A regulatory subunit B
K04382 PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04503 CCND1; G1/S-specific cyclin-D1
K05031 CFTR, ABCC7; cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6 ]
K05062 LEPR, CD295; leptin receptor
K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1 ]
K05459 IGF1; insulin-like growth factor 1
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K06276 PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1 ]
K07187 IRS2; insulin receptor substrate 2
K07191 SLC2A4, GLUT4; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 4
K07197 SREBP1, SREBF1; sterol regulatory element-binding transcription factor 1
K07198 PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31 ]
K07199 PRKAB; 5'-AMP-activated protein kinase, regulatory beta subunit
K07200 PRKAG; 5'-AMP-activated protein kinase, regulatory gamma subunit
K07201 FOXO1; forkhead box protein O1
K07202 PPARGC1A, PGC1A; alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07204 RAPTOR; regulatory associated protein of mTOR
K07205 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1
K07206 TSC1; tuberous sclerosis 1
K07207 TSC2; tuberous sclerosis 2
K07208 RHEB; Ras homolog enriched in brain
K07292 NR2A1, HNF4A; hepatocyte nuclear factor 4-alpha
K07296 ADIPOQ, ACDC; adiponectin
K07297 ADIPOR; adiponectin receptor
K07359 CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 [EC:2.7.11.17 ]
K07877 RAB2A; Ras-related protein Rab-2A
K07881 RAB14; Ras-related protein Rab-14
K07901 RAB8A, MEL; Ras-related protein Rab-8A
K07903 RAB10; Ras-related protein Rab-10
K07905 RAB11B; Ras-related protein Rab-11B
K08271 STRADA, LYK5; STE20-related kinase adapter protein alpha
K08272 CAB39, MO25; calcium binding protein 39
K08530 NR1C3, PPARG; peroxisome proliferator-activated receptor gamma
K08765 CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21 ]
K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5
K09048 CREB3; cyclic AMP-responsive element-binding protein 3
K09408 FOXO3; forkhead box protein O3
K11411 SIRT1, SIR2L1; NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286 ]
K11583 PPP2R3; serine/threonine-protein phosphatase 2A regulatory subunit B''
K11584 PPP2R5; serine/threonine-protein phosphatase 2A regulatory subunit B'
K13088 ELAVL1, HUR; ELAV-like protein 1
K16172 IRS1; insulin receptor substrate 1
K16184 AKT1S1, PRAS40; proline-rich AKT1 substrate 1
K16333 CRTC2, TORC2; CREB-regulated transcription coactivator 2
K17445 IRS3; insulin receptor substrate 3
K17446 IRS4; insulin receptor substrate 4
K17532 STRADB; STE20-related kinase adapter protein beta
K18341 TBC1D1; TBC1 domain family member 1
K19523 CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21 ]
K19524 CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21 ]
K25893 CIDEA; cell death activator CIDE-A
Compound C00354 D-Fructose 1,6-bisphosphate
C00665 beta-D-Fructose 2,6-bisphosphate
C00668 alpha-D-Glucose 6-phosphate
C01172 beta-D-Glucose 6-phosphate
C04677 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C09731 Epigallocatechin gallate
Reference Authors Steinberg GR, Kemp BE
Title AMPK in Health and Disease.
Journal Reference Authors Hardie DG.
Title The AMP-activated protein kinase pathway--new players upstream and downstream.
Journal Reference Authors Russo GL, Russo M, Ungaro P
Title AMP-activated protein kinase: a target for old drugs against diabetes and cancer.
Journal Reference Authors Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S
Title AMPK in the brain: its roles in energy balance and neuroprotection.
Journal Reference Authors Li J, McCullough LD
Title Effects of AMP-activated protein kinase in cerebral ischemia.
Journal Reference 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 Reference 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 Reference Authors Shackelford DB, Shaw RJ
Title The LKB1-AMPK pathway: metabolism and growth control in tumour suppression.
Journal Reference Authors Chung JH, Manganiello V, Dyck JR
Title Resveratrol as a calorie restriction mimetic: therapeutic implications.
Journal Reference 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 Reference Authors Towler MC, Hardie DG
Title AMP-activated protein kinase in metabolic control and insulin signaling.
Journal Reference Authors Richter EA, Hargreaves M
Title Exercise, GLUT4, and skeletal muscle glucose uptake.
Journal Reference 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 Reference Authors Minokoshi Y, Toda C, Okamoto S
Title Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle.
Journal Reference Authors Guggino WB, Stanton BA
Title New insights into cystic fibrosis: molecular switches that regulate CFTR.
Journal Reference Authors Cheng A, Saltiel AR
Title More TORC for the gluconeogenic engine.
Journal Reference 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 Reference Authors Morris DL, Rui L
Title Recent advances in understanding leptin signaling and leptin resistance.
Journal Reference Authors Minokoshi Y, Shiuchi T, Lee S, Suzuki A, Okamoto S
Title Role of hypothalamic AMP-kinase in food intake regulation.
Journal Reference 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 Related ko00010 Glycolysis / Gluconeogenesis
ko00500 Starch and sucrose metabolism
ko01040 Biosynthesis of unsaturated fatty acids
ko04920 Adipocytokine signaling pathway
