AKT phosphorylation sites of Ser473 and Thr308 regulate AKT degradation
AKT phosphorylation sites of Ser473 and Thr308 regulate AKT degradation
复制标题
Ser473 和 Thr308 的 AKT 磷酸化位点调节 AKT 降解
DOI：
10.1080/09168451.2018.1549974
复制
发表时间：
2019-03
影响因子：
1.6
通讯作者：
Jin Xiaoxia
中科院分区：
文献类型：
--
作者：
Wei Yingze;Zhou Jianyun;Yu Haiyan;Jin Xiaoxia
蛋白激酶B（AKT）是一种丝氨酸-苏氨酸激酶，在多种人类疾病中介导多种细胞过程。磷酸化一直是AKT翻译后修饰研究最多的领域，近年来人们对磷酸化与泛素化之间的联系进行了探索。AKT的泛素化是其磷酸化和活化的重要步骤，但磷酸化AKT是否调节其泛素化状态仍不清楚。在本研究中，我们模拟脱磷酸化的AKT通过使用诱变技术在Thr 308和Ser 473到丙氨酸（AKT-2A）。在失去磷酸化活性后，AKT增强其降解并阻止其在胰岛素刺激后从质膜释放。第四，AKT-2A被发现通过泛素-蛋白酶体途径降解，这表明AKT在Ser 473和Thr 308位点的非磷酸化增加了其泛素化水平。因此，AKT在Ser 473和Thr 308位点的磷酸化对其泛素化状态有显著影响。缩略语：AKT：蛋白激酶B;序列号：丝氨酸;阈值：苏氨酸;如果有：免疫荧光;促红细胞生成素：环氧霉素; Baf：巴弗洛霉素;公共广播公司：磷酸盐缓冲液图解摘要AKT在Ser 473和Thr 308位点失去磷酸化活性后，其降解能力增强，通过泛素-蛋白酶体途径降解。
ABSTRACT Protein kinase B (AKT) is a serine-threonine kinase that mediates diverse cellular processes in a variety of human diseases. Phosphorylation is always the best studied posttranslational modification of AKT and a connection between phosphorylation and ubiquitination has been explored recently. Ubiquitination of AKT is an important step for its phosphorylation and activation, while whether phosphorylated AKT regulated its ubiquitination status is still unknow. In the present study, we mimic dephosphorylation of AKT by using mutagenesis techniques at both Thr308 and Ser473 into Alanine (AKT-2A). After losing phosphorylation activity, AKT enhances its degradation and prevents itself release from the plasma membrane after insulin stimulation. Fourthermore, AKT-2A is found to be degraded through ubiquitin- proteasome pathway which declared that un-phosphorylation of AKT at both Ser473 and Thr308 sites increases its ubiquitination level. In conclusion, AKT phosphorylated at Ser473 and Thr308 sites have a significant effect on its ubiquitination status. Abbreviations: AKT: Protein kinase B; Ser: serine; Thr: threonine; IF: immunofluorescence; Epo: Epoxomicin; Baf: Bafilomycin; PBS: phosphate buffer solution Graphical Abstract After losing phosphorylation activity at both Ser473 and Thr308 sites, AKT enhances its degradation and degraded through ubiquitin-proteasome pathway.
登录
查看更多内容
DOI：
10.1080/19381980.2017.1356518
发表时间：
2017
期刊：
Dermato-endocrinology
影响因子：
--
作者：
Mirdamadi Y;Bommhardt U;Goihl A;Guttek K;Zouboulis CC;Quist S;Gollnick H
通讯作者：
Gollnick H
影响因子：
11.4
作者：
Lin, HK;Wang, L;Chang, CS
通讯作者：
Chang, CS
DOI：
10.1126/science.1175065
发表时间：
2009-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yang WL;Wang J;Chan CH;Lee SW;Campos AD;Lamothe B;Hur L;Grabiner BC;Lin X;Darnay BG;Lin HK
通讯作者：
Lin HK
影响因子：
44.1
作者：
Bae, Seunghee;Kim, Sun-Yong;An, Sungkwan
通讯作者：
An, Sungkwan
影响因子：
16.6
作者：
Finley D
通讯作者：
Finley D