Hart Jonathan R, Vogt Peter K
The Scripps Research Institute, Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Oncotarget. 2011 Jun;2(6):467-76. doi: 10.18632/oncotarget.293.
Akt (cellular homolog of murine thymoma virus akt8 oncogene) is an essential component of the PI3K (phosphatidylinositol 3-kinase) pathway. Its activity is stimulated by receptor tyrosine kinases and G-protein coupled receptors and plays a critical role in the regulation of cell proliferation, differentiation and apoptosis. A gain of function in Akt can lead to uncontrolled cell proliferation and resistance to apoptosis, both hallmarks of oncogenic transformation. In this communication, we have investigated the phosphorylation at the Akt residues T308, S473 and T450 and their roles in oncogenic transformation and signaling. We find that T450 phosphorylation has only a minimal part in these activities. In contrast, the phosphorylation of T308 and of S473 fulfills essential, distinct, and non-overlapping functions that we define with inactivating and with phosphomimetic mutations of these sites.
Akt（鼠胸腺瘤病毒akt8癌基因的细胞同源物）是PI3K（磷脂酰肌醇3激酶）信号通路的重要组成部分。其活性受受体酪氨酸激酶和G蛋白偶联受体的刺激，在细胞增殖、分化和凋亡的调控中起关键作用。Akt功能的获得可导致细胞不受控制地增殖和对凋亡的抵抗，这两者都是致癌转化的标志。在本通讯中，我们研究了Akt残基T308、S473和T450的磷酸化及其在致癌转化和信号传导中的作用。我们发现T450磷酸化在这些活动中只起很小的作用。相反，T308和S473的磷酸化发挥着重要的、独特的且不重叠的功能，我们通过这些位点的失活突变和磷酸模拟突变来定义这些功能。
