General Information:

Id: 559
Diseases: Cancer
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Peutz-Jeghers syndrome - [OMIM]
Mammalia
article
Reference: Shaw RJ et al.(2004) The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc. Natl. Acad. Sci. U.S.A. 101: 3329-3335 [PMID: 14985505]

Interaction Information:

Comment Wild-type, but not kinase-dead, LKB1 immunoprecipitated from mammalian cells efficiently phosphorylated a bacterially expressed MBP fusion product of the AMPK alpha catalytic subunit in vitro.
Formal Description
Interaction-ID: 2901

gene/protein

STK11

increases_phosphorylation of

gene/protein

AMPK alpha chain

in vitro
Comment Coexpression of LKB1 with STRAD led to a dramatic proportional increase in LKB1 autophosphorylation and transphosphorylation of MBP-AMPK alpha.
Formal Description
Interaction-ID: 2968

complex/PPI

STK11-STRAD complex

increases_phosphorylation of

gene/protein

STK11

via autophosphorylation
Comment Coexpression of LKB1 with STRAD led to a dramatic proportional increase in LKB1 autophosphorylation and transphosphorylation of MBP-AMPK alpha.
Formal Description
Interaction-ID: 2970

complex/PPI

STK11-STRAD complex

increases_phosphorylation of

gene/protein

AMPK alpha chain

Comment In vitro phosphorylation of AMPK by wild-type LKB1 alone or STRAD-activated LKB1 induced the kinase activity of AMPK by an average of 27- and 50-fold, respectively. Kinase-dead LKB1 alone or coexpressed with STRAD was unable to activate AMPK.
Formal Description
Interaction-ID: 2971

gene/protein

STRAD

NOT affects_phosphorylation of

complex/PPI

AMPK

Comment LKB1 kinase activity was not directly stimulated in vitro by AMP.
Formal Description
Interaction-ID: 2972

drug/chemical compound

AMP

NOT increases_activity of

gene/protein

STK11

in vitro
Comment The kinase activity of LKB1 immunoprecipitated from cells treated with peroxide or AICAR was not increased compared with that from untreated control cells, as measured both by autophosphotylation and transphpsphorylation or the MBP-AMPK fusion.
Formal Description
Interaction-ID: 2975

drug/chemical compound

H2O2

NOT increases_activity of

gene/protein

STK11

Comment The kinase activity of LKB1 immunoprecipitated from cells treated with peroxide or AICAR was not increased compared with that from untreated control cells, as measured both by autophosphotylation and transphpsphorylation or the MBP-AMPK fusion.
Formal Description
Interaction-ID: 2978

drug/chemical compound

AICAR

NOT increases_activity of

gene/protein

STK11

Drugbank entries Show/Hide entries for AICAR
Comment Peroxide or AICAR treatment led to activation of AMPK in vivo, which supports the model in which allosteric regulation or the AMPK heterotrimer by AMP-binding allows it to better serve as substrate for the upstream kinase, as opposed to direct regulation of the activity of the AMPK kinase by AMP.
Formal Description
Interaction-ID: 2979

drug/chemical compound

H2O2

increases_activity of

complex/PPI

AMPK

in vivo
Comment Peroxide or AICAR treatment led to activation of AMPK in vivo, which supports the model in which allosteric regulation or the AMPK heterotrimer by AMP-binding allows it to better serve as substrate for the upstream kinase, as opposed to direct regulation of the activity of the AMPK kinase by AMP.
Formal Description
Interaction-ID: 2981

drug/chemical compound

AICAR

increases_activity of

complex/PPI

AMPK

in vivo
Drugbank entries Show/Hide entries for AICAR
Comment AMPK inactivates ACC through phosphorylation of Ser-79, thereby stimulating fatty acid oxidation. LKB1-deficient murine embryonic fibroblasts show nearly complete loss of AMPK phosphorylation and ACC phosphorylation in response to stimuli that activate AMPK (peroxide and AICAR).
Formal Description
Interaction-ID: 2983

complex/PPI

AMPK

decreases_activity of

gene/protein

ACACA

via phosphorylation at Ser79 of ACC
Drugbank entries Show/Hide entries for ACACA
Comment LKB1-deficient cells are hypersensitive to apoptosis induced by energy stress.
Formal Description
Interaction-ID: 2994

gene/protein

STK11

affects_activity of

Comment In murine embryonic fibroblasts metformin activated AMPK, this response was ablated in the LKB1-deficient cells.
Formal Description
Interaction-ID: 2995

drug/chemical compound

Metformin

increases_activity of

complex/PPI

AMPK

in MEF cells
Drugbank entries Show/Hide entries for Metformin
Comment In murine embryonic fibroblasts metformin activated AMPK, this response was ablated in the LKB1-deficient cells.
Formal Description
Interaction-ID: 2996

drug/chemical compound

Metformin

NOT increases_activity of

complex/PPI

AMPK

in LKB1-deficient MEF cells
Drugbank entries Show/Hide entries for Metformin
Comment LKB1 protects cells from apoptosis induced by agents that elevate intracellular AMP.
Formal Description
Interaction-ID: 2997

gene/protein

STK11

decreases_activity of

induced by elevated AMP
Comment AMPK inactivates ACC through phosphorylation of Ser-79, thereby stimulating fatty acid oxidation. LKB1-deficient murine embryonic fibroblasts show nearly complete loss of AMPK phosphorylation and ACC phosphorylation in response to stimuli that activate AMPK (peroxide and AICAR).
Formal Description
Interaction-ID: 12836

complex/PPI

AMPK

increases_activity of

via inhibition of ACC