scholarly journals Ribosomal Protein S6 Kinase Is a Critical Downstream Effector of the Target of Rapamycin Complex 1 for Long-term Facilitation inAplysia

2010 ◽  
Vol 285 (16) ◽  
pp. 12255-12267 ◽  
Author(s):  
Daniel B. Weatherill ◽  
John Dyer ◽  
Wayne S. Sossin
Keyword(s):  
Ribosomal Protein ◽  
Target Of Rapamycin ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Downstream Effector ◽  
Long Term Facilitation ◽  
Ribosomal Protein S6 Kinase

scholarly journals Phosphoproteomic Analysis of Neonatal Regenerative Myocardium Revealed Important Roles of Checkpoint Kinase 1 via Activating Mammalian Target of Rapamycin C1/Ribosomal Protein S6 Kinase b-1 Pathway

Circulation ◽  
2020 ◽  
Vol 141 (19) ◽  
pp. 1554-1569 ◽  
Author(s):  
Yi Fan ◽  
Yiwei Cheng ◽  
Yafei Li ◽  
Bingrui Chen ◽  
Zimu Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ribosomal Protein ◽  
Mammalian Target Of Rapamycin ◽  
Border Zone ◽  
Target Of Rapamycin ◽  
Cardiomyocyte Proliferation ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Ribosomal Protein S6 Kinase

Background: In mammals, regenerative therapy after myocardial infarction is hampered by the limited regenerative capacity of adult heart, whereas a transient regenerative capacity is maintained in the neonatal heart. Systemic phosphorylation signaling analysis on ischemic neonatal myocardium might be helpful to identify key pathways involved in heart regeneration. Our aim was to define the kinase-substrate network in ischemic neonatal myocardium and to identify key pathways involved in heart regeneration after ischemic insult. Methods: Quantitative phosphoproteomics profiling was performed on infarct border zone of neonatal myocardium, and kinase-substrate network analysis revealed 11 kinases with enriched substrates and upregulated phosphorylation levels, including checkpoint kinase 1 (CHK1) kinase. The effect of CHK1 on cardiac regeneration was tested on Institute of Cancer Research CD1 neonatal and adult mice that underwent apical resection or myocardial infarction. Results: In vitro, CHK1 overexpression promoted whereas CHK1 knockdown blunted cardiomyocyte proliferation. In vivo, inhibition of CHK1 hindered myocardial regeneration on resection border zone in neonatal mice. In adult myocardial infarction mice, CHK1 overexpression on infarct border zone upregulated mammalian target of rapamycin C1/ribosomal protein S6 kinase b-1 pathway, promoted cardiomyocyte proliferation, and improved cardiac function. Inhibiting mammalian target of rapamycin activity by rapamycin blunted the neonatal cardiomyocyte proliferation induced by CHK1 overexpression in vitro. Conclusions: Our study indicates that phosphoproteome of neonatal regenerative myocardium could help identify important signaling pathways involved in myocardial regeneration. CHK1 is found to be a key signaling responsible for neonatal regeneration. Myocardial overexpression of CHK1 could improve cardiac regeneration in adult hearts by activating the mammalian target of rapamycin C1/ribosomal protein S6 kinase b-1 pathway. Thus, CHK1 might serve as a potential novel target in myocardial repair after myocardial infarction.

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

Planta Medica ◽  
2018 ◽  
Vol 84 (16) ◽  
pp. 1183-1190 ◽  
Author(s):  
Huajiao Chen ◽  
Daohua Shi ◽  
Peiguang Niu ◽  
Yanting Zhu ◽  
Jintuo Zhou
Keyword(s):  
Ribosomal Protein ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Nuclear Factor Kappab ◽  
Pyrrolidine Dithiocarbamate ◽  
Nuclear Factor ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Anti Inflammatory ◽  
Ribosomal Protein S6 Kinase

AbstractCardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-α, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition.

The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-α in 3T3-L1 adipocytes and is a target for transactivation by PPARγ

2006 ◽  
Vol 291 (1) ◽  
pp. E115-E127 ◽  
Author(s):  
Ji Young Kim ◽  
Kristin Tillison ◽  
Jun-Ho Lee ◽  
David A. Rearick ◽  
Cynthia M. Smas
Keyword(s):  
Adipose Tissue ◽  
Ribosomal Protein ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
S6 Kinase ◽  
Triglyceride Lipase ◽  
Ribosomal Protein S6 ◽  
Tnf Α ◽  
Adipose Tissue Triglyceride ◽  
Ribosomal Protein S6 Kinase

The minimal adipose phenotype of hormone-sensitive lipase (HSL)-null mice suggested that other hormonally responsive lipase(s) were present in adipocytes. Recent studies have characterized a new adipose tissue triglyceride lipase, ATGL/PNPLA2/destnutrin/iPLA2ζ/TTS2.2 (ATGL). We had previously cloned a novel adipose-enriched transcript by differential screening and recently determined its identity with murine ATGL. We report here on the regulation of ATGL by TNF-α and insulin in 3T3-L1 adipocytes and identify ATGL as a target for transcriptional activation by the key adipogenic transcription factor PPARγ. Insulin at 100 nM resulted in a marked decrease in ATGL transcript that was effectively blocked by inhibitors for PI 3-kinase and p70 ribosomal protein S6 kinase. TNF-α treatment decreased ATGL transcript in a time-dependent manner that paralleled TNF-α downregulation of PPARγ with a maximal decrease noted by 6 h. TNF-α effects on ATGL were attenuated by pretreatment with PD-98059, LY-294002, or rapamycin, suggesting involvement of the p44/42 MAP kinase, PI 3-kinase, and p70 ribosomal protein S6 kinase signals. To study transcriptional regulation of ATGL, we cloned 2,979 bp of the murine ATGL 5′-flanking region. Compared with promoterless pGL2-Basic, the −2979/+21 ATGL luciferase construct demonstrated 120- and 40-fold increases in activity in white and brown adipocytes, respectively. Luciferase reporter activities for a series of eight ATGL promoter deletions revealed that the −928/+21, −1738/+21, −1979/+21, and −2979/+21 constructs were transactivated by PPARγ. Our findings identify the novel lipase ATGL to be a target gene for TNF-α and insulin action in adipocytes and reveal that it is subject to transcriptional control by PPARγ-mediated signals.

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