General Information:

Id: 575
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
article
Reference: Woods A et al.(2005) Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2: 21-33 [PMID: 16054096]

Interaction Information:

Comment Cultured mouse embryonic fibroblasts (MEFs) isolated from LKB1-/- embryos were subjected either to oxidative stress (hydrogen peroxide, H2O2) or hyperosmotic stress (sorbitol), in both cases AMPK activity was markedly increased in LKB1-/- MEFs relative to untreated cells.
Formal Description
Interaction-ID: 3013

drug/chemical compound

H2O2

increases_activity of

complex/PPI

AMPK

in LKB1-/- MEF cells
Comment Cultured mouse embryonic fibroblasts (MEFs) isolated from LKB1-/- embryos were subjected either to oxidative stress (hydrogen peroxide, H2O2) or hyperosmotic stress (sorbitol), in both cases AMPK activity was markedly increased in LKB1-/- MEFs relative to untreated cells.
Formal Description
Interaction-ID: 3031

drug/chemical compound

Sorbitol

increases_activity of

complex/PPI

AMPK

in LKB1-/- MEF cells
Comment Ionomycin (Ca2+ ionophore) treatment of HeLa cells, which lack LKB1, activated AMPK over 10-fold relative to untreated cells.
Formal Description
Interaction-ID: 3033

drug/chemical compound

Ionomycin

increases_activity of

complex/PPI

AMPK

in HeLa cells
Comment Hydrogen peroxide treatment of HeLa cells activated AMPK 3-fold.
Formal Description
Interaction-ID: 3034

drug/chemical compound

H2O2

increases_activity of

complex/PPI

AMPK

in HeLa cells
Comment STO-609, an inhibitor of CaMKK, caused a dose-dependent reduction in the activation of AMPK by ionomycin in HeLa cells.
Formal Description
Interaction-ID: 3035

drug/chemical compound

STO-609

decreases_activity of

gene/protein

CAMKK

Comment Ca2+ regulates the activity of AMPK.
Formal Description
Interaction-ID: 3036

drug/chemical compound

Ca2+

affects_activity of

complex/PPI

AMPK

Comment AMPK is activated by phosphorylation in the absence of LKB1, thus another AMPK kinase exists. CaMKK-alpha and CaMKK-beta were expressed in CCL13 cells, which do not express LKB1, expression of CaMKK-beta but not CaMKK-alpha led to a dramatic increase in AMPK activity.
Formal Description
Interaction-ID: 3037

gene/protein

CAMKK1

NOT increases_activity of

complex/PPI

AMPK

in CCL13 cells overexpressing CaMKK1
Comment CaMKK-alpha and CaMKK-beta were expressed in CCL13 cells, which do not express LKB1, expression of CaMKK-beta but not CaMKK-alpha led to a dramatic increase in AMPK activity.
Formal Description
Interaction-ID: 3038

gene/protein

CAMKK2

increases_activity of

complex/PPI

AMPK

in CCL13 cells overexpressing CaMKK2
Comment Pharmacological inhibition of CaMKK, or downregulation of CaMKK-beta using RNA interference, almost completely abolishes AMPK activation.
Formal Description
Interaction-ID: 3039

gene/protein

CAMKK2

affects_activity of

complex/PPI

AMPK

Comment CaMKK-beta isolated from rat brain or expressed in E. coli phosphorylates and activates AMPK in vitro via phosphorylation of Thr172 of the AMPK alpha chain.
Formal Description
Interaction-ID: 3040

gene/protein

CAMKK2

increases_activity of

complex/PPI

AMPK

in vitro
Comment CaMKK-beta isolated from rat brain or expressed in E. coli phosphorylates and activates AMPK in vitro via phosphorylation of Thr172 of the AMPK alpha chain.
Formal Description
Interaction-ID: 3044

gene/protein

CAMKK2

increases_phosphorylation of

gene/protein

AMPK alpha chain

in vitro, at Thr172 of AMPK alpha chain
Comment AMPK is regulated by at least two upstream kinases, CaMKK and LKB1, and AMPK may play a role in Ca2+-mediated signal transduction pathways.
Formal Description
Interaction-ID: 3045

complex/PPI

AMPK

affects_activity of

Comment STO-609, an inhibitor of CaMKK, caused a dose-dependent reduction in the activation of AMPK by ionomycin in HeLa cells.
Formal Description
Interaction-ID: 12837

drug/chemical compound

STO-609

decreases_activity of

complex/PPI

AMPK

after ionomycin activation