EphA receptors form a complex with caspase-8 to induce apoptotic cell death.
EphA receptors form a complex with caspase-8 to induce apoptotic cell death.
复制标题
DOI：
10.14348/molcells.2015.2279
复制
发表时间：
2015-04
影响因子：
3.8
通讯作者：
Park S
中科院分区：
文献类型：
--
作者：
Lee H;Park S;Kang YS;Park S
EphA7参与了神经上皮细胞凋亡的调控。在这份报告中，我们提供了EphA7与caspase-8相互作用以诱导细胞凋亡信号的证据。首先，使用生物素化的ePhinA5-Fc的下拉实验表明，EphA7与野生型caspase-8或催化失活的caspase-8突变体共沉淀。第二，在单独表达EphA7或caspase-8不影响细胞存活或凋亡的实验条件下，EphA7与caspase-8共转染显著增加caspase-3裂解阳性细胞的数量。EphA4在caspase-8诱导细胞凋亡中也起作用，而EphA8不起作用。第三，caspase-8的催化活性是细胞凋亡信号级联所必需的，而EphA4受体的酪氨酸激酶活性不是必需的。有趣的是，我们发现激酶失活的EphA4与催化失活的caspase-8很好地共存于质膜上，这表明这些突变蛋白之间的相互作用更稳定。最后，我们观察到EphA7受体的胞外区是与caspase-8相互作用的关键区域，而EphA7的胞内区则不是。因此，我们认为Eph受体与跨膜蛋白物理结合形成一个凋亡信号复合体，这种未知的受体样蛋白作为Eph受体和caspase-8之间的生化连接物。
EphA7 has been implicated in the regulation of apoptotic cell death in neural epithelial cells. In this report, we provide evidence that EphA7 interacts with caspase-8 to induce apoptotic cell signaling. First, a pull-down assay using biotinylated ephrinA5-Fc showed that EphA7 co-precipitated with wild type caspase-8 or catalytically inactive caspase-8 mutant. Second, co-transfection of EphA7 with caspase-8 significantly increased the number of cleaved caspase-3 positive apoptotic cells under an experimental condition where transfection of EphA7 or caspase-8 alone did not affect cell viability or apoptosis. EphA4 also had a causative role in inducing apoptotic cell death with caspase-8, whereas EphA8 did not. Third, caspase-8 catalytic activity was essential for the apoptotic signaling cascade, whereas tyrosine kinase activity of the EphA4 receptor was not. Interestingly, we found that kinase-inactive EphA4 was well co-localized at the plasma membrane with catalytically inactive caspase-8, suggesting that an interaction between these mutant proteins was more stable. Finally, we observed that the extracellular region of the EphA7 receptor was critical for interacting with caspase-8, whereas the cytoplasmic region of EphA7 was not. Therefore, we propose that Eph receptors physically associate with a transmembrane protein to form an apoptotic signaling complex and that this unidentified receptor-like protein acts as a biochemical linker between the Eph receptor and caspase-8.
登录
查看更多内容
影响因子：
64.8
作者：
Zhang, JK;Cado, D;Winoto, A
通讯作者：
Winoto, A
影响因子：
64.5
作者：
Hsu, HL;Shu, HB;Goeddel, DV
通讯作者：
Goeddel, DV
影响因子：
32.4
作者：
Hsu, HL;Huang, JN;Goeddel, DV
通讯作者：
Goeddel, DV
影响因子：
5.3
作者：
Shin, Jongdae;Gu, Changkyu;Park, Soochul
通讯作者：
Park, Soochul
影响因子：
12.4
作者：
Park, E.;Kim, Y.;Park, S.
通讯作者：
Park, S.