Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils
Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils
复制标题
DOI：
10.1074/jbc.m400063200
复制
发表时间：
2004-05-14
影响因子：
4.8
通讯作者：
Henson, PM
中科院分区：
文献类型：
--
作者：
Gardai, SJ;Hildeman, DA;Henson, PM
虽然重要的细胞凋亡，Bax的调节机制知之甚少。本研究表明Ser（184）的磷酸化调节Bax活性。磷酸化需要磷脂酰肌醇3-激酶/Akt活化，并且似乎由Akt本身介导。在丝氨酸磷酸化形式中，Bax在细胞质中被检测到，不能与活化特异性抗体6A 7免疫沉淀，并促进与Mcl-1、Bcl-x（L）和A1的异源二聚化。凋亡的中性粒细胞具有丝氨酸磷酸化Bax的水平降低，与激活Bax的增加以及发现易位到线粒体的Bax的量的增加相关。我们认为Bax是由丝氨酸（184）的磷酸化以Akt依赖的方式调节的，并且磷酸化通过维持与抗凋亡Bcl-2家族成员异源二聚化的蛋白质在细胞质中抑制Bax对线粒体的作用。
Although important for apoptosis, the mechanism of Bax regulation is poorly understood. This study demonstrates that phosphorylation of Ser(184) regulates Bax activity. The phosphorylation required phosphatidylinositol 3-kinase/Akt activation and appeared to be mediated by Akt itself. In the serine-phosphorylated form, Bax was detected in the cytoplasm, could not be immunoprecipitated with the activation-specific antibody 6A7, and promoted heterodimerization with Mcl-1, Bcl-x(L), and A1. Apoptotic neutrophils possessed reduced levels of serine-phosphorylated Bax correlating with an increase in activated Bax as well as an increase in the amount of Bax found translocated to the mitochondria. We suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members.