General Information:

Id: 519
Diseases: Cardiomyopathy, hypertrophic
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Metabolic syndrome
Peutz-Jeghers syndrome - [OMIM]
Wolff-Parkinson-White syndrome - [OMIM]
Mammalia
review
Reference: Carling D et al.(2008) The regulation of AMP-activated protein kinase by upstream kinases. Int J Obes (Lond) 32: S55-S59 [PMID: 18719600]

Interaction Information:

Comment Mutations in the human AMPK gamma-2 chain isoform cause cardiac hypertrophy due to massive glycogen accumulation, together with Wolff-Parkinson-White syndrome, a preexcitation disorder.
Formal Description
Interaction-ID: 2571

gene/protein mutant

PRKAG2-mut

increases_activity of

disease

Cardiomyopathy, hypertrophic

Comment Mutations in the human AMPK gamma-2 chain isoform cause cardiac hypertrophy due to massive glycogen accumulation, together with Wolff-Parkinson-White syndrome, a preexcitation disorder.
Formal Description
Interaction-ID: 2576

gene/protein mutant

PRKAG2-mut

increases_activity of

Comment Activation of AMPK requires phosphorylation of threonine 172 (Thr-172) within the catalytic alpha subunit.
Formal Description
Interaction-ID: 2577

process

phosphorylation

increases_activity of

complex/PPI

AMPK

at Thr172 of AMPK alpha chain
Comment Mutations in the gene coding for LKB1 lead to a cancer predisposition syndrome in humans called Peutz-Jeghers syndrome.
Formal Description
Interaction-ID: 2578

gene/protein mutant

STK11-mut

increases_activity of

Comment AMP inhibits dephosphorylation of AMPK by protein phosphatases.
Formal Description
Interaction-ID: 2583

drug/chemical compound

AMP

increases_activity of

complex/PPI

AMPK

via inhibition of dephosphorylation of AMPK by protein phosphatases
Comment LKB1, like AMPK, is a heterotrimeric kinase and requires binding of MO25 and STE-20 related adaptor protein for activity. LKB1 is the predominant upstream kinase for AMPK alpha-2 activation in skeletal muscle and heart, but other kinases act on AMPK alpha-1 in these tissues.
Formal Description
Interaction-ID: 2585

complex/PPI

STK11-STRAD alpha/beta-MO25 alpha/beta complex

increases_activity of

gene/protein

PRKAA2

in skeletal muscle, in cardiac muscle
Comment LKB1 is the predominant upstream kinase for both AMPK alpha-1 and alpha-2 in liver.
Formal Description
Interaction-ID: 2587

complex/PPI

STK11-STRAD alpha/beta-MO25 alpha/beta complex

increases_activity of

gene/protein

PRKAA2

in liver
Comment Ca(2+)/calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) phosphorylates and activates AMPK.
Formal Description
Interaction-ID: 2588

gene/protein

CAMKK2

increases_activity of

complex/PPI

AMPK

Comment Ca(2+)/calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) phosphorylates and activates AMPK.
Formal Description
Interaction-ID: 2590

gene/protein

CAMKK2

increases_phosphorylation of

complex/PPI

AMPK

Comment AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a major role in maintaining energy homoeostasis.
Formal Description
Interaction-ID: 2591

complex/PPI

AMPK

affects_activity of

Comment AMPK is activated by a rise in the AMP/ATP ratio that occurs following a fall in ATP levels.
Formal Description
Interaction-ID: 2593

phenotype

decreased intracellular ATP level

increases_activity of

complex/PPI

AMPK

Comment AMPK is also regulated by the adipokines, adiponectin and leptin, hormones that are secreted from adipocytes.
Formal Description
Interaction-ID: 2594

gene/protein

ADIPOQ

affects_activity of

complex/PPI

AMPK

Comment AMPK is also regulated by the adipokines, adiponectin and leptin, hormones that are secreted from adipocytes.
Formal Description
Interaction-ID: 2595

gene/protein

LEP

affects_activity of

complex/PPI

AMPK

Comment AMPK regulates a wide range of metabolic pathways, including fatty acid oxidation, fatty acid synthesis, glycolysis and gluconeogenesis.
Formal Description
Interaction-ID: 2596

complex/PPI

AMPK

affects_activity of

Comment AMPK regulates a wide range of metabolic pathways, including fatty acid oxidation, fatty acid synthesis, glycolysis and gluconeogenesis.
Formal Description
Interaction-ID: 2597

complex/PPI

AMPK

affects_activity of

Comment AMPK regulates a wide range of metabolic pathways, including fatty acid oxidation, fatty acid synthesis, glycolysis and gluconeogenesis.
Formal Description
Interaction-ID: 2598

complex/PPI

AMPK

affects_activity of

Comment AMPK regulates a wide range of metabolic pathways, including fatty acid oxidation, fatty acid synthesis, glycolysis and gluconeogenesis.
Formal Description
Interaction-ID: 2599

complex/PPI

AMPK

affects_activity of

process

gluconeogenesis

Comment In peripheral tissues, activation of AMPK leads to responses that are beneficial in counteracting the deleterious effects that arise in the metabolic syndrome.
Formal Description
Interaction-ID: 2600

complex/PPI

AMPK

affects_activity of

disease

Metabolic syndrome

Comment A decrease in hypothalamic AMPK activity is associated with decreased feeding, whereas activation of AMPK leads to increased food intake.
Formal Description
Interaction-ID: 2601

complex/PPI

AMPK

increases_activity of

Comment Signalling pathways occurring in the hypothalamus lead to changes in AMPK activity in peripheral tissues, such as skeletal muscle, via the sympathetic nervous system.
Formal Description
Interaction-ID: 2603

tissue/cell line

sympathetic nervous system

affects_activity of

complex/PPI

AMPK

Comment LKB1 is the predominant upstream kinase for AMPK alpha-2 activation in skeletal muscle and heart, but other kinases act on AMPK alpha-1 in these tissues.
Formal Description
Interaction-ID: 12797

complex/PPI

STK11-STRAD alpha/beta-MO25 alpha/beta complex

NOT increases_activity of

gene/protein

PRKAA1

in skeletal muscle, in cardiac muscle
Drugbank entries Show/Hide entries for PRKAA1
Comment LKB1 is the predominant upstream kinase for both AMPK alpha-1 and alpha-2 in liver.
Formal Description
Interaction-ID: 12798

complex/PPI

STK11-STRAD alpha/beta-MO25 alpha/beta complex

increases_activity of

gene/protein

PRKAA1

in liver
Drugbank entries Show/Hide entries for PRKAA1