Oncogenic transformation induced by membrane-targeted Akt2 and Akt3
Oncogenic transformation induced by membrane-targeted Akt2 and Akt3
复制标题
DOI：
10.1038/sj.onc.1204486
复制
发表时间：
2001-07-19
期刊：
影响因子：
8
通讯作者：
Aoki, M
中科院分区：
文献类型：
--
作者：
Mende, I;Malstrom, S;Aoki, M
激酶 Akt2、Akt3 及其肉豆蔻酰化变体 Myr-Akt2 和 Myr-Akt3 由 RCAS 载体在鸡胚成纤维细胞 (CEF) 中表达，Myr-Akt2 和 Myr-Akt3 具有强致癌性，可诱导转化细胞的多层病灶。相比之下，野生型Akt2和Akt3的转化能力较差，其焦点形成效率低100倍以上；病灶出现较晚，且多层结构较少。添加肉豆蔻酰化信号不仅增强了致癌潜力，而且还增加了激酶活性。 Myr-Akt2 和 Myr-Akt3 也在动物中诱导血管肉瘤，而野生型 Akt2 和 Akt3 在体内不致癌。此外，在转基因小鼠中，Akt2 由 lck（淋巴细胞特异性激酶）启动子驱动，诱导淋巴瘤。此处描述的 Akt2 和 Akt3 的致癌作用与 Akt1 的致癌作用无法区分。因此，与致癌转化相关的下游靶点可能由这三种 Akt 激酶共享。
The kinases Akt2, Akt3 and their myristylated variants, Myr-Akt2 and Myr-Akt3 were expressed by the RCAS vector in chicken embryo fibroblasts (CEF), Myr-Akt2 and Myr-Akt3 were strongly oncogenic, inducing multilayered foci of transformed cells. In contrast, wild-type Akt2 and Akt3 were only poorly transforming, their efficiencies of focus formation were more than 100-fold lower; foci appeared later and showed less multilayering, Addition of the myristylation signal not only enhanced oncogenic potential hut also increased kinase activities. Myr-Akt2 and Myr-Akt3 also induced hemangiosarcomas in the animal, whereas wild type Akt2 and Akt3 were not oncogenic in vivo. Furthermore, Akt2, driven by the lck (lymphocyte specific kinase) promoter in transgenic mice, induced lymphomas, The oncogenic effects of Akt2 and Akt3 described here are indistinguishable from those of Akt1, The downstream targets relevant to oncogenic transformation are therefore probably shared by the three Akt kinases.