Raptor-rictor axis in TGFβ-induced protein synthesis

Das, Falguni; Ghosh‐Choudhury, Nandini; Mahimainathan, Lenin; Venkatesan, Balachandar; Féliers, Denis; Riley, David S.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh

doi:10.1016/j.cellsig.2007.10.027

Cited by 61 publications

(162 citation statements)

References 91 publications

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“…High glucose recruits mTORC1 to promote protein synthesis and hypertrophy in kidney epithelial and mesangial cells (13,19,35,(52)(53)(54). One mechanism by which mTOR complex 1 is stimulated by high glucose in the GECs involves inhibition of AMPK phosphorylation and activity (12,13).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Lee

Mariappan

Féliers

et al. 2012

Journal of Biological Chemistry

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112

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Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Lee

Mariappan

Féliers

et al. 2012

Journal of Biological Chemistry

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112

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“…Cell Culture and Adenovirus Infection-Normal rat glomerular mesangial cells were grown in DMEM with low glucose containing 17% fetal bovine serum in the presence of penicillin and streptomycin, as described previously (17). At confluence, the cells were washed with PBS, and serum-free medium was added for 24 h. The cells were then incubated with DMEM with 25 mM glucose for the indicated times.…”

Section: Methodsmentioning

confidence: 99%

“…Ad CMV catalase (Ad Catalase) was purchased from the Gene Transfer Vector Core (University of Iowa). Adenovirus vectors expressing dominant negative PI 3 kinase, PTEN, and HA-tagged dominant negative Akt have been described previously (7,17). The luciferase reporter plasmid 8xFKTK-Luc containing eight copies of the FoxO binding element has been described previously (18).…”

Section: Methodsmentioning

confidence: 99%

“…For osmotic control, DMEM with 5 mM glucose plus 20 mM mannitol was used. When necessary, the cells were infected with adenovirus vectors at a multiplicity of infection of 50 for 24 h, essentially as described previously (17). Adenovirus vectors containing green fluorescence protein (Ad GFP) or ␤-galactosidase (Ad ␤-Gal) were used as controls.…”

Section: Methodsmentioning

confidence: 99%

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High Glucose Forces a Positive Feedback Loop Connecting Akt Kinase and FoxO1 Transcription Factor to Activate mTORC1 Kinase for Mesangial Cell Hypertrophy and Matrix Protein Expression

Das

Ghosh‐Choudhury

Dey

et al. 2014

Journal of Biological Chemistry

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“…Several mTOR functions are executed via its downstream targets, namely the 70-kDa ribosomal protein S6 kinase I (p70S6K), which is directly activated by mTOR through phosphorylation at the Thr-389 site (16 -19), and the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), an inhibitor or protein translation whose function is reduced when phosphorylated by mTOR (11). Notably, the steady-state levels of p70S6K phosphorylated at Thr-389 are often used as an indirect measurement of mTOR output as they greatly correlate with mTOR activity (16,18,19). mTOR activity is physiologically regulated by extracellular stimuli (e.g.…”

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confidence: 99%

Naturally Secreted Amyloid-β Increases Mammalian Target of Rapamycin (mTOR) Activity via a PRAS40-mediated Mechanism

Caccamo¹,

Maldonado²,

Majumder³

et al. 2011

Journal of Biological Chemistry

159

132

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Reducing the mammalian target of rapamycin (mTOR) activity increases lifespan and health span in a variety of organisms. Alterations in protein homeostasis and mTOR activity and signaling have been reported in several neurodegenerative disorders, including Alzheimer disease (AD); however, the causes of such deregulations remain elusive. Here, we show that mTOR activity and signaling are increased in cell lines stably transfected with mutant amyloid precursor protein (APP) and in brains of 3xTg-AD mice, an animal model of AD. In addition, we show that in the 3xTg-AD mice, mTOR activity can be reduced to wild type levels by genetically preventing A␤ accumulation. Similarly, intrahippocampal injections of an anti-A␤ antibody reduced A␤ levels and normalized mTOR activity, indicating that high A␤ levels are necessary for mTOR hyperactivity in 3xTg-AD mice. We also show that the intrahippocampal injection of naturally secreted A␤ is sufficient to increase mTOR signaling in the brains of wild type mice. The mechanism behind the A␤-induced mTOR hyperactivity is mediated by the proline-rich Akt substrate 40 (PRAS40) as we show that the activation of PRAS40 plays a key role in the A␤-induced mTOR hyperactivity. Taken together, our data show that A␤ accumulation, which has been suggested to be the culprit of AD pathogenesis, causes mTOR hyperactivity by regulating PRAS40 phosphorylation. These data further indicate that the mTOR pathway is one of the pathways by which A␤ exerts its toxicity and further support the idea that reducing mTOR signaling in AD may be a valid therapeutic approach.Amyloid plaques and neurofibrillary tangles are hallmark neuropathological lesions of Alzheimer disease (AD), 3 the most common form of neurodegenerative disorder (1). Neurofibrillary tangles are intracellular inclusions formed of hyperphosphorylated Tau (2-4). Plaques are extracellular inclusions mainly formed of a small peptide called amyloid-␤ (A␤) (5, 6). Clinically, AD is characterized by profound memory loss and cognitive dysfunction (7). Growing evidence is converging on soluble A␤ as a mediator of early cognitive decline in AD (8, 9). Although the molecular mechanisms underlying A␤-induced cognitive decline remain elusive, soluble A␤ oligomers have been shown to alter signal transduction pathways that are key for learning and memory, suggesting that alterations in such pathways may underlie the onset of cognitive decline in AD (10).The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that forms two multiprotein complexes known as mTOR complex (mTORC) 1 and 2 (11). mTORC1 controls protein homeostasis; its activity is inhibited by rapamycin, and it contains mTOR, raptor, proline-rich Akt substrate 40 kDa (PRAS40), and mLT8. mTORC2, which is insensitive to rapamycin, controls cellular shape by modulating actin function and contains mTOR, rictor, mLST8, and hSIN (11, 12). In mTORC1, raptor binds to mTOR substrates and is necessary for mTOR activity (13). PRAS40 is another mTOR regulatory protein, which inhibits mTOR...

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Raptor-rictor axis in TGFβ-induced protein synthesis

Cited by 61 publications

References 91 publications

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

High Glucose Forces a Positive Feedback Loop Connecting Akt Kinase and FoxO1 Transcription Factor to Activate mTORC1 Kinase for Mesangial Cell Hypertrophy and Matrix Protein Expression

Naturally Secreted Amyloid-β Increases Mammalian Target of Rapamycin (mTOR) Activity via a PRAS40-mediated Mechanism

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