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AMPK phosphorylation of raptor mediates a metabolic checkpoint.

Molecular cell | Apr 25, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18439900

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 mTORC1 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.

Pubmed ID: 18439900 RIS Download

Mesh terms: AMP-Activated Protein Kinases | Adaptor Proteins, Signal Transducing | Amino Acid Motifs | Animals | Apoptosis | Cell Cycle | Cell Line | Humans | Male | Mice | Mice, Inbred Strains | Multienzyme Complexes | Multiprotein Complexes | Peptide Library | Phosphorylation | Protein-Serine-Threonine Kinases | Proteins | Proteomics | Serine | Substrate Specificity | TOR Serine-Threonine Kinases | Transcription Factors

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM079498
  • Agency: NCI NIH HHS, Id: P01 CA120964
  • Agency: NCI NIH HHS, Id: P01 CA120964
  • Agency: NCI NIH HHS, Id: P01 CA120964-02
  • Agency: NIDDK NIH HHS, Id: R01 DK080425
  • Agency: NIDDK NIH HHS, Id: R01 DK080425
  • Agency: NIDDK NIH HHS, Id: R01 DK080425-02
  • Agency: NIGMS NIH HHS, Id: R01 GM079498
  • Agency: NIGMS NIH HHS, Id: R01 GM079498-02
  • Agency: NCI NIH HHS, Id: T32 CA009370
  • Agency: NCI NIH HHS, Id: T32 CA009370
  • Agency: NCI NIH HHS, Id: T32 CA009370-26

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