Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling
Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling
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DOI：
10.1074/jbc.m110.166991
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发表时间：
2011-02-25
影响因子：
4.8
通讯作者：
Luis Rosa, Jose
中科院分区：
文献类型：
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作者：
Tato, Irantzu;Bartrons, Ramon;Luis Rosa, Jose
哺乳动物雷帕霉素靶蛋白（mTOR）复合物的活性调节基本的细胞过程，如生长、增殖或存活。营养素如氨基酸是mTOR复合物1（mTORC 1）激活的重要调节剂，从而影响细胞生长、蛋白质合成和自噬。在这里，我们表明，氨基酸也可以激活mTOR复合物2（mTORC 2）。这种激活由I类PI 3 K和Akt的活性介导。氨基酸诱导Akt在Thr-308和Ser-473处的快速磷酸化。尽管两种磷酸化都依赖于mTOR的存在，但只有Ser-473处的Akt磷酸化依赖于mTORC 2的特定组分rictor的存在。激酶测定证实mTORC 2通过氨基酸活化。这种信号传导是功能性的，如Akt底物FOXO 3a的磷酸化所证明的。有趣的是，使用不同的饥饿条件，氨基酸可以选择性地激活mTORC 1或mTORC 2。这些发现确定了氨基酸使用的新信号通路，强调了这些营养素在细胞代谢中的至关重要性，并提供了新的机制见解。
The activity of mammalian target of rapamycin (mTOR) complexes regulates essential cellular processes, such as growth, proliferation, or survival. Nutrients such as amino acids are important regulators of mTOR complex 1 (mTORC1) activation, thus affecting cell growth, protein synthesis, and autophagy. Here, we show that amino acids may also activate mTOR complex 2 (mTORC2). This activation is mediated by the activity of class I PI3K and of Akt. Amino acids induced a rapid phosphorylation of Akt at Thr-308 and Ser-473. Whereas both phosphorylations were dependent on the presence of mTOR, only Akt phosphorylation at Ser-473 was dependent on the presence of rictor, a specific component of mTORC2. Kinase assays confirmed mTORC2 activation by amino acids. This signaling was functional, as demonstrated by the phosphorylation of Akt substrate FOXO3a. Interestingly, using different starvation conditions, amino acids can selectively activate mTORC1 or mTORC2. These findings identify a new signaling pathway used by amino acids underscoring the crucial importance of these nutrients in cell metabolism and offering new mechanistic insights.