Hepatitis B virus X protein activates a survival signaling by linking Src to phosphatidylinositol 3-kinase
Hepatitis B virus X protein activates a survival signaling by linking Src to phosphatidylinositol 3-kinase
复制标题
DOI：
10.1074/jbc.m302580200
复制
发表时间：
2003-08-22
影响因子：
4.8
通讯作者：
Doong, SL
中科院分区：
文献类型：
--
作者：
Shih, WL;Kuo, ML;Doong, SL
我们先前已经证明，反式激活熟练的乙肝病毒X蛋白(HBX)通过激活磷脂酰肌醇3-激酶(PI 3-K)/Akt信号通路来保护Hep 3B细胞免受转化生长因子-β(TGF-β)诱导的细胞凋亡。本工作进一步研究了HBx是如何激活PI3-激酶的。在Hep 3B细胞中表达反式激活的HBx或HBx-GFP融合蛋白后，SRC活性增加。Src家族激酶抑制剂PP2和C-末端Src激酶(CSK)均可减轻HBx介导的PI 3-激酶的激活，并保护其免受转化生长因子-β诱导的细胞凋亡。因此，HBx通过将Src连接到PI3-Kinase来激活生存信号。系统亚细胞分离和膜漂浮分析表明，异位表达的HBxGFP中，约有1.5%与Src所在的周质膜有关。然而，无论是核靶向还是胞膜靶向的HBxGFP都不能上调Src活性，也不能增强PI3K生存信号通路。
We have previously shown that transactivation-proficient hepatitis virus B X protein (HBx) protects Hep 3B cells from transforming growth factor-beta (TGF-beta)-induced apoptosis via activation of the phosphatidylinositol 3-kinase ( PI 3-kinase)/Akt signaling pathway. This work further investigated how HBx activates PI 3-kinase. Src activity was elevated in Hep 3B cells following expression of transactivation-proficient HBx or HBx-GFP fusion proteins. The Src family kinase inhibitor PP2 and C-terminal Src kinase (Csk) both alleviated HBx-mediated PI 3-kinase activation and protection from TGF-beta-induced apoptosis. Therefore, HBx activated a survival signal by linking Src to PI 3-kinase. Systemic subcellular fractionation and membrane flotation assays indicated that similar to 1.5% of ectopically expressed HBxGFP was associated with periplasmic membrane where Src was located. However, neither nucleus-targeted nor periplasmic membrane-targeted HBxGFP was able to upregulate Src activity or to augment PI 3-kinase survival signaling pathway.