mSin1 is required for mTORC2 assembly and Akt Ser473 phosphorylation; isoforms define distinct complexes.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Mammalian cells |
| Journal | Current biology : CB |
| Year | 2006 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cub.2006.08.001 · PMID 16919458 |
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that participates in at least two distinct multiprotein complexes, mTORC1 and mTORC2 . These complexes play important roles in the regulation of cell growth, proliferation, survival, and metabolism. mTORC2 is a hydrophobic motif kinase for the cell-survival protein Akt/PKB and, here, we identify mSin1 as a component of mTORC2 but not mTORC1. mSin1 is necessary for the assembly of mTORC2 and for its capacity to phosphorylate Akt/PKB. Alternative splicing generates at least five isoforms of the mSin1 protein , three of which assemble into mTORC2 to generate three distinct mTORC2s. Even though all mTORC2s can phosphorylate Akt/PKB in vitro, insulin regulates the activity of only two of them. Thus, we propose that cells contain several mTORC2 flavors that may phosphorylate Akt/PKB in response to different signals.
| Intervention | Biochemical/genetic (mSin1) |
| Target | mTORC2 / mSin1 / Akt |
| Model | Mammalian cells |
| Effect | mSin1 is required for Akt/PKB phosphorylation; its isoforms define three distinct mTORC2 complexes |