期刊
MOLECULAR BIOLOGY OF THE CELL
卷 23, 期 15, 页码 2955-2962出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E11-12-1034
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资金
- American Diabetes Association Mentor-Based Postdoctoral Fellowship
- National Institutes of Health [5R01DK061618, DK060597, 1R01DK083491, 1R01GM5040316]
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-C2 alpha, 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-C2 alpha 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.
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