Ignet

Gene Information

Gene symbol: STK11

Gene name: serine/threonine kinase 11

HGNC ID: 11389

Synonyms: PJS, LKB1

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	ADIPOQ	1 hits
3	AKT1	1 hits
4	ATIC	1 hits
5	CAT	1 hits
6	CREB1	1 hits
7	CRTC2	1 hits
8	INS	1 hits
9	MAS1	1 hits
10	NUAK2	1 hits
11	PCK2	1 hits
12	POMC	1 hits
13	PPARGC1A	1 hits
14	PRKAA1	1 hits
15	PRKAA2	1 hits
16	PRKCZ	1 hits
17	PTEN	1 hits
18	SLC37A4	1 hits
19	SLC47A1	1 hits
20	SMARCB1	1 hits
21	SOD1	1 hits
22	TPR	1 hits

Related Sentences

#	PMID	Sentence
1	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
2	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
3	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
4	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
5	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
6	16054041	AMPK is regulated by upstream kinases of which the tumor suppressor, LKB1, is the first to be identified.
7	16407220	These data suggest that LKB1 is required for PKCzeta-enhanced AMPK activation.
8	16407220	In vitro, recombinant PKCzeta phosphorylated LKB1 at Ser428, resulting in phosphorylation of AMPK at Thr172.
9	16407220	Further, direct mutation of Ser428 of LKB1 into alanine, like the kinase-inactive LKB1 mutant, abolished ONOO- -induced AMPK activation.
10	16966378	These results demonstrate that skeletal muscle LKB1 is a negative regulator of insulin sensitivity and glucose homeostasis.
11	16966378	LKB1-mediated TRB3 expression provides a novel link between LKB1 and Akt, critical kinases involved in both tumor genesis and cell metabolism.
12	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
13	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
14	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
15	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
16	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
17	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
18	17652778	LKB1 (Par-4) is required for normal activation of AMPK in the liver and also regulates cell polarity.
19	17652778	Demonstration that metformin, a common drug for Type 2 diabetes, requires LKB1 for full therapeutic benefit has increased interest in AMPK signaling.
20	17875968	Interestingly, the ONOO(-)-enhanced PTEN phosphorylation and Akt inhibition can be blocked by LKB1-specific small interfering RNA.
21	17875968	Consistently, LKB1 phosphorylated PTEN at Ser380/Thr382/383 in vitro, suggesting that LKB1 might act as an upstream kinase for PTEN.
22	17875968	Finally, treatment with Tempol, a superoxide dismutase mimetic, and insulin, both of which reduced the ONOO- formation, markedly reduced diabetes-enhanced LKB1-Ser428 phosphorylation, PTEN, and apoptosis in the endothelium of mouse aortas.
23	17875968	We conclude that hyperglycemia triggers apoptosis by inhibiting Akt signaling via ONOO(-)-mediated LKB1-dependent PTEN activation.
24	17855357	Phosphorylation of AMPK and ACC in response to A-769662 is also abolished in isolated mouse skeletal muscle lacking LKB1, a major upstream kinase for AMPK in this tissue.
25	17855357	However, in HeLa cells, which lack LKB1 but express the alternate upstream kinase calmodulin-dependent protein kinase kinase-beta, phosphorylation of AMPK and ACC in response to A-769662 still occurs.
26	18321849	Conversely, ONOO(-) inhibited Akt Ser(473) phosphorylation when wild type LKB1 were reintroduced in HeLa S3 cells.
27	18321849	Further analysis revealed that PKCzeta directly phosphorylated LKB1 at Ser(428) in vitro and in intact cells, resulting in increased PTEN phosphorylation at Ser(380)/Thr(382/383).
28	18321849	We conclude that PKCzeta mediates LKB1-dependent Akt inhibition in response to ONOO(-), resulting in endothelial apoptosis.
29	18387000	The LKB1 tumour suppressor phosphorylates and activates AMPK (AMP-activated protein kinase) when cellular energy levels are low, thereby suppressing growth through multiple pathways, including inhibiting the mTORC1 (mammalian target of rapamycin complex 1) kinase that is activated in the majority of human cancers.
30	18387000	We demonstrate that inhibition of AMPK resulting from a hypomorphic mutation that decreases LKB1 expression does not lead to tumorigenesis on its own, but markedly accelerates tumour development in PTEN(+/-) mice.
31	18387000	We demonstrate that LKB1 is required for activators of AMPK to inhibit mTORC1 signalling as well as cell growth in PTEN-deficient cells.
32	18435912	We report that a synthetic structural isomer of dihydrocapsiate, isodihydrocapsiate (8-methylnonanoic acid 3-hydroxy-4-methoxy benzyl ester) improves type 2 diabetes by activating AMPK through the LKB1 pathway.
33	19447226	In addition, phosphorylation of LKB1, which is a tumor-suppressor protein and a major AMPK-kinase, was increased by catechin treatment.
34	19447226	EGCG-induced phosphorylation of LKB1 and AMPKalpha was suppressed by treatment with catalase, suggesting that reactive oxygen species are involved in EGCG-induced activation of the LKB1/AMPK pathway.
35	20460103	We found that ascofuranone improves ER stress-induced insulin resistance by activating AMPK through the LKB1 pathway.
36	20460103	Ascofuranone-induced phosphorylation of AMPK and ACC was not increased in A549 cells lacking LKB1.
37	20357370	We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.
38	20441792	LKB1 is a kinase that is required for activation of AMP-activated protein kinase (AMPK) as well as 13 AMPK-related protein kinases.
39	20577053	Metformin decreased expression of the gene encoding the catalytic subunit of glucose-6-phosphatase (G6Pase), while cytosolic phosphoenolpyruvate carboxykinase (Pepck) gene expression was unaffected in wild-type, AMPK-deficient, and LKB1-deficient hepatocytes.
40	20682687	We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter.
41	20713714	Muscle contraction increased sucrose nonfermenting AMPK-related kinase (SNARK) activity, an effect blunted in the muscle-specific LKB1 knockout mice.
42	20956520	CDDO-Me activates AMP-activated protein kinase (AMPK) and via LKB1 activation in muscle and liver in vivo.
43	20142099	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues, and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.
44	21349801	Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK.
45	16308421	The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase].
46	16308421	The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity.
47	16308421	In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered the nucleus, driving the expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), which in turn drives gluconeogenesis.
48	16308421	Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1alpha expression and normalized blood glucose levels in mice with deleted liver LKB1, indicating that TORC2 is a critical target of LKB1/AMPK signals in the regulation of gluconeogenesis.
49	21266325	LKB1, the Peutz-Jeghers syndrome gene product, and Ca(2+)-calmodulin-dependent protein kinase kinase ? (CaMKK?) are key upstream activators of AMPK.
50	21266325	This phenotype contrasts with that seen in mice lacking AMPK in POMC neurons with defects in body-weight regulation but not glucose homeostasis, which suggests that LKB1 plays additional functions distinct from activating AMPK in POMC neurons.
51	18063812	In addition, direct mutagenesis of either Ser428 or Ser307 of LKB1 into alanine, like the kinase-dead LKB1 mutant, abolished both TPr-stimulated AMPK activation and coimmunoprecipitation.
52	18063812	We conclude that TPr stimulation triggers reactive oxygen species-mediated LKB1-dependent AMPK activation, which in return inhibits cellular protein synthesis in VSMCs.
53	18250273	Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1.
54	18250273	Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells.
55	18250273	Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation.
56	18250273	Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells.
57	18250273	We conclude that PKC-zeta phosphorylates LKB1 at Ser428, resulting in LKB1 nuclear export and hence AMPK activation.
58	20354156	LKB1 phosphorylates AMP-activated protein kinase (AMPK) and several related protein kinases.
59	21606593	Furthermore, in primary mouse hepatocytes, the absence of LKB1, AMPK, or the transcriptional coactivator CRTC2 did not prevent adiponectin from inhibiting glucose output or reducing gluconeogenic gene expression.
60	21357941	These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders.
61	21631893	The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation.