Activation of mTORC2 by association with the ribosome
- PMID: 21376236
- DOI: 10.1016/j.cell.2011.02.014
Activation of mTORC2 by association with the ribosome
Abstract
The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of growth. Mammalian TOR complex 2 (mTORC2) regulates AGC kinase family members and is implicated in various disorders, including cancer and diabetes. Here, we investigated the upstream regulation of mTORC2. A genetic screen in yeast and subsequent studies in mammalian cells revealed that ribosomes, but not protein synthesis, are required for mTORC2 signaling. Active mTORC2 was physically associated with the ribosome, and insulin-stimulated PI3K signaling promoted mTORC2-ribosome binding, suggesting that ribosomes activate mTORC2 directly. Findings with melanoma and colon cancer cells suggest that mTORC2-ribosome association is important in oncogenic PI3K signaling. Thus, TORC2-ribosome interaction is a likely conserved mechanism of TORC2 activation that is physiologically relevant in both normal and cancer cells. As ribosome content determines growth capacity of a cell, this mechanism of TORC2 regulation ensures that TORC2 is active only in growing cells.
Copyright © 2011 Elsevier Inc. All rights reserved.
Comment in
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The ribosome and TORC2: collaborators for cell growth.Cell. 2011 Mar 4;144(5):640-2. doi: 10.1016/j.cell.2011.02.029. Cell. 2011. PMID: 21376227 Free PMC article.
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