AMPK phosphorylation of raptor mediates a metabolic checkpoint
- PMID: 18439900
- PMCID: PMC2674027
- DOI: 10.1016/j.molcel.2008.03.003
AMPK phosphorylation of raptor mediates a metabolic checkpoint
Abstract
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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f4.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f5.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f6.gif)
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2674027/bin/nihms100815f7.gif)
Comment in
-
AMPK and Raptor: matching cell growth to energy supply.Mol Cell. 2008 May 9;30(3):263-5. doi: 10.1016/j.molcel.2008.04.012. Mol Cell. 2008. PMID: 18471972
Similar articles
-
LKB1 and AMP-activated protein kinase control of mTOR signalling and growth.Acta Physiol (Oxf). 2009 May;196(1):65-80. doi: 10.1111/j.1748-1716.2009.01972.x. Epub 2009 Feb 19. Acta Physiol (Oxf). 2009. PMID: 19245654 Free PMC article. Review.
-
The association of AMPK with ULK1 regulates autophagy.PLoS One. 2010 Nov 3;5(11):e15394. doi: 10.1371/journal.pone.0015394. PLoS One. 2010. PMID: 21072212 Free PMC article.
-
Alcohol and PRAS40 knockdown decrease mTOR activity and protein synthesis via AMPK signaling and changes in mTORC1 interaction.J Cell Biochem. 2010 Apr 15;109(6):1172-84. doi: 10.1002/jcb.22496. J Cell Biochem. 2010. PMID: 20127721 Free PMC article.
-
Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia.Mol Cell Biol. 2011 May;31(9):1870-84. doi: 10.1128/MCB.01393-10. Epub 2011 Mar 7. Mol Cell Biol. 2011. PMID: 21383064 Free PMC article.
-
New roles for the LKB1-->AMPK pathway.Curr Opin Cell Biol. 2005 Apr;17(2):167-73. doi: 10.1016/j.ceb.2005.01.006. Curr Opin Cell Biol. 2005. PMID: 15780593 Review.
Cited by
-
Remodelling of the translatome controls diet and its impact on tumorigenesis.Nature. 2024 Aug 14. doi: 10.1038/s41586-024-07781-7. Online ahead of print. Nature. 2024. PMID: 39143206
-
Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles.Commun Biol. 2024 Aug 10;7(1):974. doi: 10.1038/s42003-024-06679-4. Commun Biol. 2024. PMID: 39127848 Free PMC article.
-
Charting cancer's course: revealing the role of diet, exercise, and the microbiome in cancer evolution and immunotherapy response.Clin Transl Oncol. 2024 Aug 2. doi: 10.1007/s12094-024-03595-1. Online ahead of print. Clin Transl Oncol. 2024. PMID: 39095683 Review.
-
FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway.Cell Biol Toxicol. 2024 Aug 2;40(1):62. doi: 10.1007/s10565-024-09899-w. Cell Biol Toxicol. 2024. PMID: 39093497 Free PMC article.
-
Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury.J Inflamm Res. 2024 Jul 15;17:4683-4700. doi: 10.2147/JIR.S467882. eCollection 2024. J Inflamm Res. 2024. PMID: 39051049 Free PMC article. Review.
References
-
- Baena-Gonzalez E, Rolland F, Thevelein JM, Sheen J. A central integrator of transcription networks in plant stress and energy signalling. Nature. 2007;448:938–942. - PubMed
-
- Baugh LR, Sternberg PW. DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest. Curr Biol. 2006;16:780–785. - PubMed
-
- Bridges D, Moorhead GB. 14-3-3 proteins: a number of functions for a numbered protein. Sci STKE. 2005;2005:re10. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous