| Background |
The regulatory associated protein of mTOR (Raptor) was identified as an mTOR binding partner that mediates mTOR signaling to downstream targets. Raptor binds to mTOR substrates, including 4E-BP1 and p70 S6 kinase, through their TOR signaling (TOS) motifs and is required for mTOR-mediated phosphorylation of these substrates. Binding of the FKBP12-rapamycin complex to mTOR inhibits the mTOR-raptor interaction, suggesting a mechanism for rapamycin's specific inhibition of mTOR signaling. This mTOR-raptor interaction and its regulation by nutrients and/or rapamycin is dependent on a protein called GβL. GβL is also part of the rapamycin-insensitive complex between mTOR and rictor (rapamycin-insensitive companion of mTOR), and may mediate rictor-mTOR signaling to downstream targets including PKCα. Furthermore, the rictor-mTOR complex has been identified as the previously elusive PDK2 responsible for the phosphorylation of Akt/PKB on Ser473, facilitating phosphorylation of Akt/PKB on Thr308 by PDK1 and required for the full activation of Akt/PKB.Recently raptor has been identified as a direct substrate of the AMP-activated protein kinase (AMPK). AMPK phosphorylates raptor on Ser722/Ser792. This phosphorylation is essential for inhibition of the raptor-containing mTOR complex 1 (mTORC1) and induces cell cycle arrest when cells are stressed for energy. These findings suggest that raptor is a critical switch that correlates cell cycle progression with energy status.
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