Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 28 for “"mTORC2"”.
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The Regulation of Mtorc2 Kinase Activity and Complex Integrity
… <p>mammalian Target of Rapamycin Complex 2 (mTORC2) was identified as the</p> <p>main Akt Ser-473 kinase, and Ser-473 phosphorylation is required for Akt</p> <p>hyperactivation. However, the detailed mechanism of mTORC2 regulation in</p> <p>response to growth factor stimulation or cellular …
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Molecular mechanisms of signal transduction in neutrophil chemotaxis
… role of mammalian Target of Rapamycin complex 2 (mTORC2) in neutrophil chemotaxis. Lines of evidence indicate that mTORC2 is essential for the dynamics of actin cytoskeleton: depletion of mTORC2 impairs the organization of actin cytoskeleton in mammalian cells, and knockout of mTORC2 inhibit …
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Pten Signaling in Regulatory T Cells and Inflammatory Disease
… disease. Mechanistically, we linked PTEN to mTORC2-mediated control of transcriptional and metabolic programs that enforce Treg cell stability and function. Consistent with this notion, deletion of Rictor, the obligate component for mTORC2, restores Treg cell function and stability in the …
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Molecular mechanisms of mammalian cell survival and differentiation
… forms two distinct complexes known as mTORC1 and mTORC2. mTORC2 controls a wide range of cellular functions, but the regulation of its signaling remains incompletely understood. In Chapter 2, I identified XPLN, a RhoGEF, as an endogenous inhibitor of mTORC2 kinase activity towards Akt. …
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The signalling pathways allowing hormonal regulation of Na+ transport in murine collecting duct cells
… (Ieq). Selective inhibition of PI3-kinase, mTORC2 and SGK1 left ~80 % of the current intact, indicating these signalling molecules are not required for basal Na+ transport. Acute addition of insulin stimulated Ieq and this occurred with a concomitant increase in mTORC2, SGK1 and Akt …
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Molecular signaling programs underlying neutrophil polarity and chemotaxis
… of Mammalian Target of Rapamycin Complex 2 (mTORC2), in regulating assembly of the actin cytoskeleton during neutrophil chemotaxis. Depletion of Mammalian Target of Rapamycin (mTOR) and Rictor, but not Raptor, impairs actin polymerization, leading edge establishment and directional migration …
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Differential Regulation of Iress In The Aurora A Mrna By Bfgf Through The Mtor Complex to rc2 Modulates Aurora A Kinase Expression
… my data reveal that the second complex, mTORC2, mediates bFGF induced IRES activity. This study is the first demonstration that growth factors differentially regulate IRESs in the same mRNA and that this is regulated through mTORC2. Importantly, this study identifies mTORC2 as a novel …
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Role of Manganese Superoxide Dismutase in Chemotherapy-induced Oxidative Stress
… MnSOD were found to be due to inhibition of the mTORC2 complex. These results are the first to suggest that long term treatment of MCL cells with rapamycin inhibits the mTORC2 complex. By understanding the key signaling molecules and affected pathways in the anti-tumor effects of mTOR inhibitors, …
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Insights into the regulation of mTOR signaling and the consequences of pharmacological inhibition
… catalytic domain. In mammals, the TORC2 homolog mTORC2 is activated by growth factors through the lipid kinase PI3K, and is a primary effector for many of its functions, including regulation of the proliferation and survival kinase Akt/PKB. Activation of PI3K also leads to activation of mTORC1. …
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The localization of mTORC1 signaling
… which in mammals are referred to as mTORC1 and mTORC2. While significant emphasis has been placed on defining which pathways TOR controls and on how TOR activity is set, less is known about where TOR is positioned or positions its effectors to control growth. In the work described here, we …
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Molecular Mechanisms Underlying Innate Immune Kinase TBK1-Driven Oncogenic Transformation
… motif sites independently of PDK1 and mTORC2. A population of AKT is bound to components of the exocyst complex. Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, TBK1 is recruited to the exocyst, where it activates AKT. …
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The identification of the mTOR-regulated phosphoproteome and a mediator of feedback inhibition to P13K-Akt
… kinase nucleates two complexes, mTORC1 and mTORC2. Collectively, the two complexes regulate processes important for cell growth and proliferation, including protein synthesis, autophagy, metabolism, and cytoskeletal maintenance. Despite this diverse array of cellular functions, few mTOR …
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Genetic Dissection of the Exit of Pluripotency in Mouse Embryonic Stem cells by CRISPR-based Screening
… are 19 mTORC1 regulators and components of the mTORC2 complex. Deficiency in the TSC and GATOR complexes resulted in mTORC1 upregulation in consistent with previous studies. However, they showed opposite phenotype during ESC differentiation: TSC complex knockout cells showed delayed …
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Novel Mechanisms of Kinase Independent Pro-Survival Functions of EGFR in Cancer
… with RICTOR and UT2 and activation of mTORC2/Akt signaling whereas inhibition of EGFR kinase function causes non-selective macro autophagy mediated by activation of mTORC1 signaling. To further support this, we have found an EGFR downregulating peptide demonstrating the induction of …
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The Role of the Mammalian Target of Rapamycin (mTOR) in Cytotoxic T Lymphocytes
… activation. PKB activity was thus uncoupled from mTORC2 activity and explained the similar phenotype of selective mTORC1 vs combined mTORC1/2 inhibition.<br/>Collectively these experiments highlight the power of high resolution analysis of proteomes to uncover critical signalling checkpoints that …
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Dual mTOR/HDAC Inhibition: Preclinical Development of a Novel Breast Cancer Therapy
… both complexes MLN0128 that targets mTORC1 and mTORC2, and Trichostatin-A (TSA), a potent inhibitor of both class I and class II HDACs, on the viability, downstream signaling, and polysome assembly of human breast cancer cell lines of various receptor subtypes (HER2-/+ and/or ER -/+), as well as …
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USING CHEMICAL AND PROTEOMICS APPROACHES TO STUDY THE FUNCTIONS OF SIRT6 AND KRAS
… Different from well-established mTORC1 and mTORC2, KRas4a/b forms a new mTOR complex without raptor or rictor in cells.
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Investigations into the roles and molecular mechanisms of LanC-like proteins
… directly facilitating Akt phosphorylation by mTORC2. Chapter 3 describes the establishment of LanCL knockout mouse lines and the phenotypic characterization of Lancl2-/- mice. Shortened life span was observed in Lancl2-/- mice, accompanied with the symptom of cardiomyopathy. These mice also …
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Identifying genes that are required for the maintenance of pancreatic ductal adenocarcinoma
… of mTOR results in downregulation of mTORCl and mTORC2 targets, while inhibition of Raptor induces downregulation of only mTORC 1 targets. As combination therapies are likely to be more effective, we looked for a drug that could combine effectively with mTOR and Raptor. From screening several …
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Novel Insights into the Regulation and Function of SGK3
… SGK3 through two different routes, one involving mTORC2 regulation and another involving the generation of a second pool of PI(3)P via sequential dephosphorylation of PI(3,4,5)P3 by SHIP2 and INPP4A/B phosphatases. These highly versatile mechanisms of SGK3 regulation explain how the Vps34-SGK3 …
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