期刊
MOLECULAR CELL
卷 30, 期 2, 页码 214-226出版社
CELL PRESS
DOI: 10.1016/j.molcel.2008.03.003
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资金
- NCI NIH HHS [P01 CA120964, T32 CA009370-26, T32 CA009370, P01 CA120964-02] Funding Source: Medline
- NIDDK NIH HHS [R01 DK080425, R01 DK080425-02] Funding Source: Medline
- NIGMS NIH HHS [GM079498, R01 GM079498, R01 GM079498-02] Funding Source: Medline
AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain responsive to energy stress. Using a proteomic and bioinformatics approach, we sought to identify additional substrates of AMPK that mediate its effects on growth control. We report here that AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor. The phosphorylation of raptor by AMPK is required for the inhibition of ImTORC1 and cell-cycle arrest induced by energy stress. These findings uncover a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status.
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