Frias Maria A, Thoreen Carson C, Jaffe Jacob D, Schroder Wayne, Sculley Tom, Carr Steven A, Sabatini David M
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Curr Biol. 2006 Sep 19;16(18):1865-70. doi: 10.1016/j.cub.2006.08.001. Epub 2006 Aug 17.
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.
雷帕霉素哺乳动物靶蛋白（mTOR）是一种丝氨酸/苏氨酸激酶，它至少参与两种不同的多蛋白复合物，即mTORC1和mTORC2。这些复合物在细胞生长、增殖、存活和代谢的调节中发挥重要作用。mTORC2是细胞存活蛋白Akt/PKB的疏水基序激酶，在此，我们确定mSin1是mTORC2而非mTORC1的一个组成部分。mSin1对于mTORC2的组装及其磷酸化Akt/PKB的能力是必需的。可变剪接产生至少五种mSin1蛋白异构体，其中三种组装成mTORC2以产生三种不同的mTORC2。尽管所有mTORC2在体外都能磷酸化Akt/PKB，但胰岛素仅调节其中两种的活性。因此，我们提出细胞含有几种不同类型的mTORC2，它们可能响应不同信号磷酸化Akt/PKB。
