c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, is essential for tumor necrosis factor alpha-induced c-Jun kinase activation and apoptosis
c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, is essential for tumor necrosis factor alpha-induced c-Jun kinase activation and apoptosis
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DOI：
10.1128/mcb.24.24.10844-10856.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Lin, AN
中科院分区：
文献类型：
--
作者：
Liu, J;Minemoto, Y;Lin, AN
C-jun氨基末端蛋白激酶(JNK)的两种亚型JNK1和JNK2具有相同和不同的功能。然而，其分子机制尚不清楚。在这里，我们报告JNK1，而不是JNK2，在肿瘤坏死因子α(TNF-α)诱导的c-Jun激酶激活、c-Jun表达和细胞凋亡中是必不可少的。利用缺乏JNK1或JNK2的小鼠成纤维细胞，我们发现JNK1可被肿瘤坏死因子-α激活，而JNK2的激活可忽略不计。此外，JNK2通过上游激酶的“无效”磷酸化来干扰JNK1的激活。因此，依赖于JNK活性的c-jun的表达和激活在JNK1缺失细胞中受损，而在JNK2缺失细胞中增强。在JNK1缺失的成纤维细胞中，肿瘤坏死因子-α诱导的细胞凋亡也被抑制，而在JNK2缺失的成纤维细胞中，肿瘤坏死因子-α诱导的凋亡增加。因此，我们的结果为JNK亚型的不同生物学功能提供了一个分子机制。
Two ubiquitously expressed isoforms of c-Jun N-terminal protein kinase (JNK), JNK1 and JNK2, have shared functions and different functions. However, the molecular mechanism is unknown. Here we report that JNK1, but not JNK2, is essential for tumor necrosis factor alpha (TNF-alpha)-induced c-jun kinase activation, c-Jun expression, and apoptosis. Using mouse fibroblasts deficient in either Jnk1 or Jnk2, we found that JNK1 was activated by TNF-alpha, whereas JNK2 activation was negligible. In addition, JNK2 interfered with JNK1 activation via its "futile" phosphorylation by upstream kinases. Consequently, expression and activation of c-jun, which depends on JNK activity, were impaired in Jnk1 null cells but enhanced in Jnk2 null cells. TNF-alpha-induced apoptosis was also suppressed in Jnk1 null fibroblasts but increased in Jnk2 null cells. Thus, our results provide a molecular mechanism underlying the different biological functions of JNK isoforms.