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PMID |
Sentence |
1 |
15068958
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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).
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2 |
15068958
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We have also reported that LKB1 activates 11 other AMPK-related kinases.
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3 |
15068958
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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.
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4 |
15068958
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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.
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5 |
16054041
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AMPK is regulated by upstream kinases of which the tumor suppressor, LKB1, is the first to be identified.
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6 |
17652778
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LKB1 (Par-4) is required for normal activation of AMPK in the liver and also regulates cell polarity.
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7 |
17652778
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Demonstration that metformin, a common drug for Type 2 diabetes, requires LKB1 for full therapeutic benefit has increased interest in AMPK signaling.
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8 |
17855357
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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.
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9 |
18387000
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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.
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10 |
18387000
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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.
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11 |
18387000
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We demonstrate that LKB1 is required for activators of AMPK to inhibit mTORC1 signalling as well as cell growth in PTEN-deficient cells.
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12 |
18435912
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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.
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13 |
19447226
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In addition, phosphorylation of LKB1, which is a tumor-suppressor protein and a major AMPK-kinase, was increased by catechin treatment.
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14 |
20460103
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We found that ascofuranone improves ER stress-induced insulin resistance by activating AMPK through the LKB1 pathway.
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15 |
20460103
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Ascofuranone-induced phosphorylation of AMPK and ACC was not increased in A549 cells lacking LKB1.
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16 |
20441792
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LKB1 is a kinase that is required for activation of AMP-activated protein kinase (AMPK) as well as 13 AMPK-related protein kinases.
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17 |
20956520
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CDDO-Me activates AMP-activated protein kinase (AMPK) and via LKB1 activation in muscle and liver in vivo.
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18 |
21349801
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Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK.
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19 |
16308421
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The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase].
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20 |
16308421
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The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity.
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21 |
21266325
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LKB1, the Peutz-Jeghers syndrome gene product, and Ca(2+)-calmodulin-dependent protein kinase kinase ? (CaMKK?) are key upstream activators of AMPK.
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22 |
18250273
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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.
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23 |
18250273
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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.
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24 |
18250273
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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.
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25 |
18250273
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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.
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26 |
20354156
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LKB1 phosphorylates AMP-activated protein kinase (AMPK) and several related protein kinases.
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27 |
21631893
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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.
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