Mammalian target of rapamycin (mTOR) activity is regulated by assembly of two functionally distinct complexes, mTORC1 and mTORC2. In syndecan-4 (S4) null endothelial cells, mTORC2 activity is reduced, resulting in decreased Akt activation, while mTORC1 activity is increased. Levels of rictor, mLST8, and mSin-1 are unchanged in total cell lysates but decreased in the rafts of S4(-/-) endothelial cells, as is the level of PKCalpha. Expression of myristoylated-PKCalpha in S4(-/-) cells restores rictor, mLST8, and mSin-1 presence in the rafts and rescues Akt phosphorylation. PKCalpha knockdown mimics the effect of S4 deletion on mTORC2 localization and Akt activation. Reduced mTORC2 activity in S4(-/-) endothelial cells results in decreased FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4(-/-) mice. Thus, S4-dependent targeting of PKCalpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2578831 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2008.09.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
β2-Adrenergic Receptor Agonist Clenbuterol Protects Against Acute Ischemia/Reperfusion-Induced Arrhythmia by Regulation of Akt/eNOS/NO/Cx43 Signaling Pathway.
Pharmacol Res Perspect
February 2025
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ventricular arrhythmias induced by ischemia/reperfusion injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction. This study investigated the protective effects of the β2-adrenergic receptor (β2-AR) agonist clenbuterol against ischemia/reperfusion-induced arrhythmias and the underlying mechanism. Anesthetized rats were subjected to 10-min left coronary artery occlusion and 10-min reperfusion in vivo.
View Article and Find Full Text PDFLINC01224 promotes the Warburg effect in gastric cancer by activating the miR-486-5p/PI3K axis.
In Vitro Cell Dev Biol Anim
January 2025
Gastroenterology Section, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.
The Warburg effect, a common feature of solid tumors, rewires the metabolism and promotes growth, survival, proliferation, and long-term maintenance in gastric cancer (GC). We performed in vitro and in vivo studies of the pathogenesis of GC to investigate the effects and mechanism of LINC01224 in this cancer. qRT-PCR was used to measure the expression of LINC01224 or miR-486-5p in GC cells, and the expression of LINC01224 in GC tissues by FISH (Fluorescence in situ hybridization) analysis was evaluated.
View Article and Find Full Text PDFCorrection: Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 Signal Transduction Pathway.
Cell Mol Neurobiol
January 2025
Pharmacy Department, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Mitigating PM Induced Myocardial Metal Deposition Through Sodium Thiosulfate Resulted in Reduction of Cardiotoxicity and Physiological Recovery From Ischemia-Reperfusion via Mitochondrial Preservation.
Environ Toxicol
January 2025
Cardiovascular Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
The cardiovascular risks linked to PM include calcification in both vasculature and myocardial tissues, leading to structural changes and functional decline. Through the selection of a clinically proven endogenous agent, sodium thiosulfate (STS), capable of addressing PM related cardiac abnormalities, we not only address the absence of effective solutions to mitigate PM toxicity, but also provide evidence for the repurposing potential of STS in ameliorating PM induced cardiac damage. Female Wistar rats were exposed to PM (250 μg/m) for 3 h daily for 21 days.
View Article and Find Full Text PDFAlcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation.
Front Immunol
January 2025
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China.
Background: Epidemiological investigations have revealed a significant association between alcohol consumption and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Nevertheless, the potential mechanisms are still inadequately revealed. This research aimed to investigate the impact of alcohol on CP/CPPS using an animal model and to elucidate the underlying mechanisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!