Chen Y R, Meyer C F, Tan T H
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Biol Chem. 1996 Jan 12;271(2):631-4. doi: 10.1074/jbc.271.2.631.
The c-Jun N-terminal kinases (JNK) are activated by various stimuli, including UV light, interleukin-1, tumor necrosis factor-alpha (TNF-alpha), and CD28 costimulation. Induction of JNK by TNF-alpha, a strong apoptosis inducer, implies a possible role of JNK in the regulation of programmed cell death. Present studies show that lethal doses of gamma radiation (GR) induced JNK activities at the early phase of apoptosis in Jurkat T-cells. We demonstrate that JNK1 was activated by either the T-cell activation signals, anti-CD28 monoclonal antibody plus phorbol 12-myristate 13-acetate (PMA), or the apoptosis-inducing treatment, GR; however, the induction patterns were different. In contrast to the rapid and transient JNK1 activation caused by CD28 signaling plus PMA, GR induced a delayed and persistent JNK1 activation. This implies a distinct regulatory mechanism and specific function of JNK1 in irradiated cells. The nuclear and cytosolic JNK1 activities were simultaneously increased in the irradiated cells without an evident change in the protein levels. The abilities of GR to induce JNK1 activation and DNA fragmentation were correlated. Peripheral blood lymphocytes were more sensitive to GR than Jurkat cells in JNK1 induction. The responsiveness of JNK1 to GR suggests the involvement of JNK1 in the initiation of the apoptosis process.
c-Jun氨基末端激酶（JNK）可被多种刺激激活，包括紫外线、白细胞介素-1、肿瘤坏死因子-α（TNF-α）以及CD28共刺激。TNF-α作为一种强大的凋亡诱导剂，其对JNK的诱导表明JNK在程序性细胞死亡的调控中可能发挥作用。目前的研究表明，致死剂量的γ射线（GR）在Jurkat T细胞凋亡的早期阶段诱导了JNK活性。我们证明JNK1可被T细胞激活信号、抗CD28单克隆抗体加佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）或凋亡诱导处理GR激活；然而，诱导模式有所不同。与CD28信号加PMA引起的快速且短暂的JNK1激活相反，GR诱导了延迟且持续的JNK1激活。这意味着JNK1在受辐照细胞中具有独特的调节机制和特定功能。在受辐照细胞中，核内和胞质中的JNK1活性同时增加，而蛋白水平没有明显变化。GR诱导JNK1激活和DNA片段化的能力是相关的。在外周血淋巴细胞中，JNK1的诱导对GR比Jurkat细胞更敏感。JNK1对GR的反应性表明JNK1参与了凋亡过程的启动。
