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Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive

Abstract

The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.

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Figure 1: mAVO3 is a functional homologue of yeast AVO3.
Figure 2: mTORC2 is rapamycin insensitive.
Figure 3: mTOR, mLST8 and mAVO3, but not raptor, are involved in cell spreading and the assembly of F-actin fibres.
Figure 4: mTORC1 and mTORC2 have distinct effectors.
Figure 5: mTORC2 signals through a Rho-type GTPase.

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Acknowledgements

We thank A. Löschmann and W. Oppliger for technical assistance, A. Lorberg and N. Kralli for helpful discussions, R. Shioda for help with alignments and P. Houghton, G. Thomas and D. Sabatini for providing reagents. This work was supported by grants from the Cancer Research Institute (E.J.), the European Molecular Biology Organization (R.L.), Cancer Research UK (A.S. and A.H.) and the Canton of Basel and the Swiss National Science Foundation (M.N.H. and M.R.).

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Correspondence to Michael N. Hall.

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Fig. S1, Fig. S2, Fig. S3, Fig. S4 (PDF 267 kb)

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Jacinto, E., Loewith, R., Schmidt, A. et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6, 1122–1128 (2004). https://doi.org/10.1038/ncb1183

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