AMP-activated protein kinase counteracts brain-derived neurotrophic factor-induced mammalian target of rapamycin complex 1 signaling in neurons

2013 ◽  
Vol 127 (1) ◽  
pp. 66-77 ◽  
Author(s):  
Yuta Ishizuka ◽  
Naomasa Kakiya ◽  
Lee A. Witters ◽  
Noriko Oshiro ◽  
Tomoaki Shirao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Neurotrophic Factor ◽  
Mammalian Target Of Rapamycin ◽  
Brain Derived Neurotrophic Factor ◽  
Target Of Rapamycin ◽  
Amp Activated Protein Kinase

A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway

2003 ◽  
Vol 8 (1) ◽  
pp. 65-79 ◽  
Author(s):  
Naoki Kimura ◽  
Chiharu Tokunaga ◽  
Sushila Dalal ◽  
Christine Richardson ◽  
Ken-ichi Yoshino ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathway ◽  
Target Of Rapamycin ◽  
Amp Activated Protein Kinase ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

Insulin-Like Growth Factor 1/Mammalian Target of Rapamycin and AMP-Activated Protein Kinase Signaling Involved in the Effects of Metformin in the Human Endometrial Cancer

2016 ◽  
Vol 26 (9) ◽  
pp. 1667-1672 ◽  
Author(s):  
Dongge Cai ◽  
Hongli Sun ◽  
Yanhua Qi ◽  
Xiaogui Zhao ◽  
Minjuan Feng ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Growth Factor ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Pilot Trial ◽  
Plasma Concentrations ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Insulin Like Growth Factor ◽  
Amp Activated Protein Kinase

BackgroundMetformin is a well-tolerated biguanide drug used for decades to treat type 2 diabetes mellitus. In recent years, long-term administration of metformin has been found to reduce carcinogenic risk for cancers derived from various tissues. However, its cellular and molecular mechanisms of anticancer action in the endometrial cancer (EC) have not yet been fully elucidated.Patients and MethodsSixty patients diagnosed as endometrial carcinoma were grouped into (n = 30) and non-treatment mixed (n = 30) for analysis. Thirty healthy donors are control groups. We attempt to investigate the interaction of metformin, insulin-like growth factor 1 (IGF-1) expression, and phosphorylated mammalian target of rapamycin (p-mTOR) and AMP-activated protein kinase (p-AMPK).ResultsWe found that high IGF-1 plasma concentrations in women with EC were reversed by conventional antidiabetic doses of metformin in the present work. In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC.ConclusionsThis pilot trial presents biological evidence consistent with antiproliferative effects of metformin in women with EC in the clinical setting.

scholarly journals cAMP-Dependent Activation of Mammalian Target of Rapamycin (mTOR) in Thyroid Cells. Implication in Mitogenesis and Activation of CDK4

2010 ◽  
Vol 24 (7) ◽  
pp. 1453-1468 ◽  
Author(s):  
Sara Blancquaert ◽  
Lifu Wang ◽  
Sabine Paternot ◽  
Katia Coulonval ◽  
Jacques E. Dumont ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Cyclin D3 ◽  
Target Of Rapamycin ◽  
Thyroid Cells ◽  
Dependent Protein ◽  
Rat Thyroid ◽  
Amp Activated Protein Kinase

Abstract How cAMP-dependent protein kinases [protein kinase A (PKA)] transduce the mitogenic stimulus elicited by TSH in thyroid cells to late activation of cyclin D3-cyclin-dependent kinase 4 (CDK4) remains enigmatic. Here we show in PC Cl3 rat thyroid cells that TSH/cAMP, like insulin, activates the mammalian target of rapamycin (mTOR)-raptor complex (mTORC1) leading to phosphorylation of S6K1 and 4E-BP1. mTORC1-dependent S6K1 phosphorylation in response to both insulin and cAMP required amino acids, whereas inhibition of AMP-activated protein kinase and glycogen synthase kinase 3 enhanced insulin but not cAMP effects. Unlike insulin, TSH/cAMP did not activate protein kinase B or induce tuberous sclerosis complex 2 phosphorylation at T1462 and Y1571. However, like insulin, TSH/cAMP produced a stable increase in mTORC1 kinase activity that was associated with augmented 4E-BP1 binding to raptor. This could be caused in part by T246 phosphorylation of PRAS40, which was found as an in vitro substrate of PKA. Both in PC Cl3 cells and primary dog thyrocytes, rapamycin inhibited DNA synthesis and retinoblastoma protein phosphorylation induced by TSH and insulin. Although rapamycin reduced cyclin D3 accumulation, the abundance of cyclin D3-CDK4 complexes was not affected. However, rapamycin inhibited the activity of these complexes by decreasing the TSH and insulin-mediated stimulation of activating T172 phosphorylation of CDK4. We propose that mTORC1 activation by TSH, at least in part through PKA-dependent phosphorylation of PRAS40, crucially contributes to mediate cAMP-dependent mitogenesis by regulating CDK4 T172-phosphorylation.

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