The small GTPase Cdc42 initiates an apoptotic signaling pathway in Jurkat T lymphocytes
The small GTPase Cdc42 initiates an apoptotic signaling pathway in Jurkat T lymphocytes
复制标题
DOI：
10.1091/mbc.8.9.1687
复制
发表时间：
1997-09-01
影响因子：
3.3
通讯作者：
Bokoch, GM
中科院分区：
文献类型：
--
作者：
Chuang, TH;Hahn, KM;Bokoch, GM
细胞凋亡在调节免疫系统的发育和稳态中起着重要作用，但控制细胞死亡的信号通路的要素尚未得到很好的定义。当在Jurkat T细胞中表达时，活化形式的小GTdR Cdc 42诱导表现出凋亡特征的细胞死亡。Cdc 42诱导的死亡反应是通过激活蛋白激酶级联介导的，导致c-Jun氨基末端激酶（JNK）的刺激。由Cdc 42启动的细胞凋亡被JNK级联的显性负性组分和阻断ICE蛋白酶（半胱天冬酶）家族活性的试剂抑制，表明JNK激酶级联的刺激可导致半胱天冬酶活化。通常在凋亡细胞中观察到的形态学事件的序列在活化的Cdc 42的存在下被修改，这表明该GTdR可以解释在凋亡程序期间细胞骨架调节的某些方面。这些数据表明，通过它的生化和形态学事件发生在细胞凋亡过程中可能会协调调节的手段。
Apoptosis plays an important role in regulating development and homeostasis of the immune system, yet the elements of the signaling pathways that control cell death have not been well defined. When expressed in Jurkat T cells, an activated form of the small GTPase Cdc42 induces cell death exhibiting the characteristics of apoptosis. The death response induced by Cdc42 is mediated by activation of a protein kinase cascade leading to stimulation of c-Jun amino terminal kinase (JNK). Apoptosis initiated by Cdc42 is inhibited by dominant negative components of the JNK cascade and by reagents that block activity of the ICE protease (caspase) family, suggesting that stimulation of the JNK kinase cascade can lead to caspase activation. The sequence of morphological events observed typically in apoptotic cells is modified in the presence of activated Cdc42, suggesting that this GTPase may account for some aspects of cytoskeletal regulation during the apoptotic program. These data suggest a means through which the biochemical and morphological events occurring during apoptosis may be coordinately regulated.