Liu Pengda, Wang Zhiwei, Wei Wenyi
Department of Pathology; Beth Israel Deaconess Medical Center; Harvard Medical School; Boston, MA USA.
The Cyrus Tang Hematology Center; Jiangsu Institute of Hematology; The First Affiliated Hospital; Soochow University; Suzhou, PR China.
Cell Cycle. 2014;13(14):2162-4. doi: 10.4161/cc.29584. Epub 2014 Jun 16.
Aberrant hyper-activation of the protein kinase Akt plays a critical role in promoting tumorigenesis. Mechanistically, previous studies establish that phosphorylation of Akt at S473 and T308 by mTORC2 and PDK1, respectively, is necessary for its full activation, thereby having been used as Akt activation markers. Recently, we report that phosphorylation of S477 and T479 at the extreme C-terminus of Akt1 promotes Akt1 activation. We further demonstrate that Akt1 pS477 and pT479 events are governed by Cdk2/Cyclin A or mTORC2 under distinct cellular contexts such as cell cycle progression or growth stimulation conditions. Here, we summarize our major findings regarding the biological significance for pS477/pT479-mediated activation of Akt and also provide perspectives for future follow-up studies.
蛋白激酶Akt的异常过度激活在促进肿瘤发生中起关键作用。从机制上讲，先前的研究表明，分别由mTORC2和PDK1在S473和T308位点对Akt进行磷酸化是其完全激活所必需的，因此已被用作Akt激活标记。最近，我们报道Akt1极端C末端的S477和T479位点的磷酸化促进Akt1激活。我们进一步证明，在不同的细胞环境下，如细胞周期进程或生长刺激条件下，Akt1的pS477和pT479事件受Cdk2/细胞周期蛋白A或mTORC2调控。在此，我们总结了关于pS477/pT479介导的Akt激活的生物学意义的主要发现，并为未来后续研究提供了展望。
