NF-KAPPA-B ACTIVATION BY TUMOR-NECROSIS-FACTOR-ALPHA IN THE JURKAT T-CELL LINE IS INDEPENDENT OF PROTEIN KINASE-A, PROTEIN-KINASE-C, AND CA2+-REGULATED KINASES
NF-KAPPA-B ACTIVATION BY TUMOR-NECROSIS-FACTOR-ALPHA IN THE JURKAT T-CELL LINE IS INDEPENDENT OF PROTEIN KINASE-A, PROTEIN-KINASE-C, AND CA2+-REGULATED KINASES
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DOI：
10.1016/1043-4666(91)90025-9
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发表时间：
1991-05-01
期刊：
影响因子：
3.8
通讯作者：
KORNER, M
中科院分区：
文献类型：
--
作者：
FEUILLARD, J;GOUY, H;KORNER, M
核因子-κB是一种DNA结合的调节因子，能够控制包括人类免疫缺陷病毒基因在内的许多基因的转录。在T细胞中，核因子κB在佛波醇酯和细胞因子肿瘤坏死因子α(肿瘤坏死因子α)的细胞处理下被激活。在本工作中，我们研究了在人T细胞系Jurkat及其亚克隆JCT6中，肿瘤坏死因子κ激活NF-αB的分子事件，这是PKA转导途径中的一个缺陷。我们发现佛波酯和肿瘤坏死因子α都能激活核因子-κB，佛波酯的激活受钙离子内流的正向调节，而肿瘤坏死因子α的激活不受钙离子内流的影响。此外，蛋白激酶C抑制剂Stauroporin可抑制PMA的激活，但其对肿瘤坏死因子α的作用不变。肿瘤坏死因子α不能激活cAMP的产生，其信号不受cAMP激活剂的调节。此外，cAMP激活剂不能激活Jurkat细胞中的NF-κB。因此，肿瘤坏死因子α诱导的核因子-gkb的激活不是由蛋白激酶C、蛋白激酶A或钙调节的蛋白激酶等主要信号转导蛋白所介导的。此外，我们还发现，胞浆酸化通过增加NF-κB/I-α的解离而不影响NF-κB的转位步骤，促进了肿瘤坏死因子κ和蛋白激酶C的激活。
NF-κB is a DNA-binding regulatory factor able to control transcription of a number of genes, including human immunodeficiency virus (HIV) genes. In T cells, NF-κB is activated upon cellular treatment by phorbol esters and the cytokine tumor necrosis factor α (TNFα). In the present work, we investigated the molecular events leading to NF-κB activation by TNFα in a human T cell line (Jurkat) and its subclone JCT6, which presents a deficiency in the PKA transduction pathway. We found that in both cell lines, both phorbol ester and TNFα were able to activate NF-κB. Phorbol activation was positively modulated by CA1+influx while TNFα activation was not. Furthermore, while PMA activation was inhibited by the PKC inhibitor staurosporin, the TNFα effect was unchanged. TNFα did not activate cAMP production and its signal was not modulated by cAMP activators. Moreover, cAMP activators did not activate NF-κB in Jurkat cells. Thus, TNFα-induced NF-gkB activation was found to be mediated by none of the major signal-mediating kinases such as protein kinase C (PKC), protein kinase A, or Ca2-regulated kinases. Furthermore, we found that cytoplasmic acidification facilitated NF-κB activation by both TNFα and PKC, by a mechanism that increases NF-κB/IκB dissociation without afflecting the NF-κB translocation step.