raptor, rictor, or mLST8，Akt-FOXO and PKCa

Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals that mTORC2 Is Required for Signaling to Akt-FOXO and PKCa, but Not S6K1

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|核心内容：

mTOR激酶通过mTORC1和mTORC2两种不同的多蛋白复合物控制细胞的生长、增殖和存活。

两种配合物中均有mTOR和mLST8，而raptor, rictor分别是mTORC1和mTORC2的一部分。

为了研究mTORC1和mTORC2在体内的功能，我们培养了缺乏raptor, rictor或mLST8的小鼠。

就像mTOR敲除的老鼠一样，那些缺乏raptor的在发育早期就会死亡。

然而，mLST8空胚胎存活到E10.5，类似于丢失了rictor的胚胎。

mLST8是维持rictor-mTOR相互作用所必需的，而raptor-mTOR相互作用则无需mLST8（mTORC1的功能更强大，但是其组合更灵活）。而mLST8和RICTOR都是Akt/PKB和PKCa——而不是S6K1——疏水基序磷酸化所必需的（因为S6K1是mTORC1的下游）。

此外，胰岛素信号传递到FOXO3，而不是TSC2或GSK3b，需要mLST8和RICTOR。

因此，mTORC1功能在早期发育中是必不可少的，mLST8仅用于mTORC2信号，mTORC2是AktFOXO和PKCa通路的必要组成部分。

原文摘要：

 The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficient for raptor, rictor, or mLST8. Like mice null for mTOR, those lacking raptor die early in development. However, mLST8 null embryos survive until e10.5 and resemble embryos missing rictor. mLST8 is necessary to maintain the rictormTOR, but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKCa, but not S6K1. Furthermore, insulin signaling to FOXO3, but not to TSC2 or GSK3b, requires mLST8 and rictor. Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the AktFOXO and PKCa pathways.

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参考文献：Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals that mTORC2 Is Required for Signaling to Akt-FOXO and PKCa, but Not S6K1

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