Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1
Copyright policy )Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1
The kinase complex mechanistic target of rapamycin 1 (mTORC1) plays an important role in controlling growth and metabolism. We report here that the stepwise formation of phosphatidylinositol 3-phosphate (PI(3)P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P 2 ) regulates the cell type–specific activation and localization of mTORC1. PI(3)P formation depends on the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α, as well as the class III PI3K Vps34, while PI(3,5)P 2 requires the phosphatidylinositol-3-phosphate-5-kinase PIKFYVE. In this paper, we show that PIKFYVE and PI3K-C2α are necessary for activation of mTORC1 and its translocation to the plasma membrane in 3T3-L1 adipocytes. Furthermore, the mTORC1 component Raptor directly interacts with PI(3,5)P 2 . Together these results suggest that PI(3,5)P 2 is an essential mTORC1 regulator that defines the localization of the complex.
- University of Michigan–Ann Arbor United States
- University of Michigan–Flint United States
TOR Serine-Threonine Kinases, Cell Membrane, Proteins, Articles, Regulatory-Associated Protein of mTOR, Mechanistic Target of Rapamycin Complex 1, Lipid Metabolism, Class III Phosphatidylinositol 3-Kinases, Mice, Phosphatidylinositol 3-Kinases, HEK293 Cells, Phosphatidylinositol Phosphates, 3T3-L1 Cells, Multiprotein Complexes, Adipocytes, Animals, Humans, Insulin, Adaptor Proteins, Signal Transducing, Signal Transduction
TOR Serine-Threonine Kinases, Cell Membrane, Proteins, Articles, Regulatory-Associated Protein of mTOR, Mechanistic Target of Rapamycin Complex 1, Lipid Metabolism, Class III Phosphatidylinositol 3-Kinases, Mice, Phosphatidylinositol 3-Kinases, HEK293 Cells, Phosphatidylinositol Phosphates, 3T3-L1 Cells, Multiprotein Complexes, Adipocytes, Animals, Humans, Insulin, Adaptor Proteins, Signal Transducing, Signal Transduction
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