General Information:

Id: 530
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Peutz-Jeghers syndrome - [OMIM]
Mammalia
article
Reference: Hawley SA et al.(2003) Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade J. Biol. 2: 28 [PMID: 14511394]

Interaction Information:

Comment The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that acts as a 'metabolic master switch' and inhibits cell proliferation.
Formal Description
Interaction-ID: 2638

complex/PPI

AMPK

affects_activity of

Comment LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta.
Formal Description
Interaction-ID: 2639

gene/protein

STK11

interacts (colocalizes) with

gene/protein

STRADA

Comment Two AMP-activated protein kinase kinase (AMPKK) activities purified from rat liver contain LKB1, STRAD alpha and MO25 alpha, and can be immunoprecipitated using anti-LKB1 antibodies.
Formal Description
Interaction-ID: 2640

complex/PPI

STK11-STRADA-CAB39 complex

increases_phosphorylation of

complex/PPI

AMPK

Comment Both endogenous and recombinant complexes of LKB1, STRAD alpha/beta and MO25 alpha/beta activate heterotrimeric AMPK via phosphorylation of Thr172.
Formal Description
Interaction-ID: 2641

complex/PPI

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

increases_activity of

complex/PPI

AMPK

Comment Both endogenous and recombinant complexes of LKB1, STRAD alpha/beta and MO25 alpha/beta activate AMPK via phosphorylation of Thr172. Catalytically active LKB1, STRAD alpha or STRAD beta and MO25 alpha or MO25 beta are required for full activity.
Formal Description
Interaction-ID: 2642

complex/PPI

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

increases_phosphorylation of

complex/PPI

AMPK

at Thr172 of AMPK alpha chain
Comment Endogenous LKB1 that activates AMPK can not be immunoprecipitated from HeLa cells. The AMPK-activating drugs AICA riboside and phenformin do not activate AMPK in HeLa cells (which lack LKB1), but activation can be restored by stably expressing wild-type, but not catalytically inactive, LKB1.
Formal Description
Interaction-ID: 2644

gene/protein

STK11

NOT is_expressed_in

tissue/cell line

HeLa cell

Comment AICA riboside and phenformin fail to activate AMPK in immortalized fibroblasts from LKB1-knockout mouse embryos.
Formal Description
Interaction-ID: 2646

drug/chemical compound

AICAR

NOT increases_activity of

complex/PPI

AMPK

in immortalized fibroblasts from LKB1-knockout mouse embryos
Drugbank entries Show/Hide entries for AICAR
Comment AICA riboside and phenformin fail to activate AMPK in immortalized fibroblasts from LKB1-knockout mouse embryos.
Formal Description
Interaction-ID: 2648

drug/chemical compound

Phenformin

NOT increases_activity of

complex/PPI

AMPK

in immortalized fibroblasts from LKB1-knockout mouse embryos
Drugbank entries Show/Hide entries for Phenformin
Comment These results provide the first description of a physiological substrate for the LKB1 tumor suppressor and suggest that it functions as an upstream regulator of AMPK. The findings indicate that the tumors in Peutz-Jeghers syndrome could result from deficient activation of AMPK as a consequence of LKB1 inactivation.
Formal Description
Interaction-ID: 2652

gene/protein

STK11

increases_activity of

via decreased AMPK activation
Comment LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta.
Formal Description
Interaction-ID: 46075

gene/protein

STK11

interacts (colocalizes) with

gene/protein

STRADB

Comment LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta.
Formal Description
Interaction-ID: 46076

gene/protein

STK11

interacts (colocalizes) with

gene/protein

CAB39

Comment LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta.
Formal Description
Interaction-ID: 46077

gene/protein

STK11

interacts (colocalizes) with

gene/protein

CAB39L