资源环境科技发展态势分析平台

Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P-3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane. We investigated mechanisms that repress mTORC1 under conditions of growth factor deprivation. We identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P-2], synthesized by class II PI3K beta (PI3KC2 beta) at LyLEs, as a negative regulator of mTORC1, whereas loss of PI3KC2 beta hyperactivated mTORC1. Growth factor deprivation induced the association of PI3KC2 beta with the Raptor subunit of mTORC1. Local PI(3,4) P2 synthesis triggered repression of mTORC1 activity through association of Raptor with inhibitory 14-3-3 proteins. These results unravel an unexpected function for local PI(3,4)P-2 production in shutting off mTORC1.