Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity.
Target of rapamycin (TOR) is an evolutionally conserved protein kinase in eukaryotes and a central cell growth controller. TOR exists in two distinct complexes, termed TORC1 and TORC2. Mammalian TORC2 has recently been shown to possess kinase activity toward the C-terminal hydrophobic site of Akt/PKB. Here, we report that Sin1 ... is an essential component of TORC2 but not of TORC1, and functions similarly to Rictor, the defining member of TORC2, in complex formation and kinase activity. Knockdown of Sin1decreases Akt phosphorylation in both Drosophila and mammalian cells and diminishes Akt function in vivo. It also disrupts the interaction between Rictor and mTOR. Furthermore, Sin1 is required for TORC2 kinase activity in vitro. Disruption of the Rictor gene in mice results in embryonic lethality and ablates Akt phosphorylation. These data demonstrate that Sin1 together with Rictor are key components of mTORC2 and play an essential role in Akt phosphorylation and signaling.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Cytoskeleton, Drosophila, Hela Cells, Humans, Mice, Mice, Knockout, Phosphoproteins, Phosphorylation, Protein Kinases, Protein Structure, Tertiary, Proto-Oncogene Proteins c-akt, Signal Transduction, Transcription Factors
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Cytoskeleton, Drosophila, Hela Cells, Humans, Mice, Mice, Knockout, Phosphoproteins, Phosphorylation, Protein Kinases, Protein Structure, Tertiary, Proto-Oncogene Proteins c-akt, Signal Transduction, Transcription Factors
Genes Dev.
Date: Oct. 15, 2006
PubMed ID: 17043309
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