mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, Tumor, Humans, Insulin, Phosphorylation, Protein Binding, Protein Isoforms, Protein Kinases, Proto-Oncogene Proteins c-akt, Sirolimus
Adaptor Proteins, Signal Transducing, Cell Line, Tumor, Humans, Insulin, Phosphorylation, Protein Binding, Protein Isoforms, Protein Kinases, Proto-Oncogene Proteins c-akt, Sirolimus
Curr. Biol.
Date: Sep. 19, 2006
PubMed ID: 16919458
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