Global ETD Search
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Showing 1 to 15 of 15 for “"Vps34"”.
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Activation of lipid kinase VPS34 by Rab GTPases
VPS34 is a lipid kinase that uses phosphatidylinositol (PI) as a substrate to produce the signalling lipid phosphatidylinositol-3-phosphate (PI(3)P). In the cell, VPS34 has to team up with other proteins in order to increase its enzymatic activity. It forms primarily two hetero-tetrameric …
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Regulation of the Lipid Kinase VPS34 by mTOR-Mediated UVRAG Phosphorylation
The lipid kinase VPS34 is an essential mediator of multiple aspects of intracellular trafficking via the formation of phosphoinositide-3-phosphate (PI(3)P) on membranes, this is critical to mediate efficient trafficking of cargo by endocytosis. In addition, VPS34 kinase activity is essential for …
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The role of the class III phosphoinositide 3-kinase VPS34 in regulatory T cells and activated CD8+ T cells
The class III PI3-kinase VPS34 is a mediator of endocytosis, trafficking of intracellular membranes and vesicles, and autophagy in various cell types. Given its central role in key cellbiological processes, we explored whether VPS34 is critical for immune cells by generating conditional knockout …
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Cryo-EM structural exploration of human VPS34 complexes and their activation by RAB GTPases and NRBF2
VPS34 is a primordial lipid kinase that catalyses the conversion of lipid phosphatidylinositol (PI) into phosphatidylinositol-3-phosphate (PI3P) on membranes. The reaction product, PI3P, is a potent signalling lipid involved promoting autophagy, phagocytosis, and endocytic sorting in mammalian …
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Non-canonical functions of leucyl-tRNA synthetase: Mechanism of cell growth and skeletal myogenesis
… signaling by mTORC1. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. In collaboration with Dr. Mee-Sup Yoon, I identified leucyl-tRNA synthetase as a leucine sensor for the activation of …
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Biochemical and Genetic Studies of Beclin 1 Function in Autophagy
… Beclin 1 exists in a protein complex with Vps34, which is a class III phosphatidylinositol (PtdIns) 3-kinase and mediates multiple vesicle trafficking pathways including autophagy and endocytosis. However the precise role of Beclin 1 in autophagy regulation is not well understood and …
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Novel Insights into the Regulation and Function of SGK3
… is regulated by both PI3K Class I and Class III (Vps34). I next demonstrate that the Vps34 - SGK3 signalling axis is responsive to growth factor stimulation in an analogous manner to PI3K Class I-Akt signalling. This represents a previously unrecognised mode of Vps34 regulation, whereby IGF1 …
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Identification of Molecular Targets for the Treatment of the Skeletal Phenotype in Lysosomal Storage Disorders
… gene (UVRAG) protein, a member of the Beclin1/Vps34 complex. Reducing mTORC1 signaling or enhancing Beclin1/Vps34/UVRAG complex activity rescued autophagy flux in LSD chondrocytes. <i>In vivo</i>, normalization of mTORC1 signaling or pharmacological induction of Beclin1 rescued collagen levels …
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A study on non-canonical autophagy signalling
… the canonical pathway is known to activate the VPS34 complex, resulting in the formation of PI(3)P-containing autophagosomes. A failure to induce functional autophagy has been implicated in a range of neurodegenerative diseases, in which the aggregation of toxic proteins and organelles cause …
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The regulation of CD8+ T cells by nutrient availability
… CD8+ cytotoxic T cells we used an inhibitor of VPS34, a phosphoinositide 3-kinase (PI3K) class III isoform that controls T cell autophagy. A key strategy was to use mass spectrometry to explore how Vps34 signalling pathways control the proteome restructuring that occurs in amino acid deprived …
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SGK3 activity and regulation in PI3K-Akt pathway inhibitor resistance in breast cancer
… was able to induce degradation of the entire VPS34 complex to impact on downstream biology. This compound will be a useful tool within the unit and wider field to study proteins with no known ligands or validate target proteins for potential PROTAC development.<br/><br/>The second aim of my …
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Scalable methods for the discovery of autophagy and disease genes
… by mechanisms likely to involve stabilising the VPS34 complex and enabling DNM2-mediated autophagosome scission. Computational techniques such as network propagation and machine learning can help to condense large, complex data into testable predictions. We exploit these tools to develop a model …
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Autophagy and Lipid Homeostasis in C. elegans
… activity (unc-51/ULK1/2, bec-1/BECN1, vps-34/VPS34, and lgg-1/LC3I) is required for neutral lipid accumulation during development in C. elegans. Moreover, long-lived, daf-2/InR and glp-1/Notch loss of function mutants, characterized by increased lipid stores, also required autophagy to …
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TRPML1: Role In Autophagy And Potential Target To Treat Lysosomal Storage Disorders
… CaMKKβ, and the PtdIns(3)-generating enzyme VPS34. Therefore, we hypothezise that during starvation, TRPML1 activation releases lysosomal calcium that activates a calcium-depedent pathway involving CaMKKβ and the induction of two essential protein complexes involved in autophagy initiation …