INDUCTION OF THE TRANSCRIPTION FACTORS NF-KB, AP-1 AND NF-AT DURING B-CELL STIMULATION THROUGH THE CD40 RECEPTOR
INDUCTION OF THE TRANSCRIPTION FACTORS NF-KB, AP-1 AND NF-AT DURING B-CELL STIMULATION THROUGH THE CD40 RECEPTOR
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DOI：
10.1093/intimm/7.2.151
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发表时间：
1995-02-01
影响因子：
4.4
通讯作者：
ROTHSTEIN, TL
中科院分区：
文献类型：
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作者：
FRANCIS, DA;KARRAS, JG;ROTHSTEIN, TL
为了阐述可能独特表征CD40介导的信号传导的要素，在CD40配体（CD40L）和抗Ig抗体刺激B细胞后，对三种转录因子的核表达进行了评估。发现交联的CD40L能诱导核因子-κB（NF - κB）、激活蛋白-1（AP - 1）和活化T细胞核因子（NF - AT）的核表达，其时间进程和强度与抗Ig所产生的相似。对NF - κB更详细的研究表明，CD40介导的DNA结合复合物的表达与反式激活活性的诱导相关，在CD40和膜表面免疫球蛋白（sIg）交联后，反式激活活性再次达到相似水平。尽管通过CD40和sIg触发的转录因子诱导具有显著相似性，但所利用的细胞内信号传导途径存在明显差异，因为蛋白激酶C（PKC）的缺失并不影响CD40介导的NF - κB诱导，而抗Ig的诱导却被消除。这些结果表明，对于两种不同的受体可能存在一种“最终共同途径”或转录因子诱导的汇聚，尽管使用了在PKC水平上不同的独立细胞内信号传导途径，但每种受体都能够单独触发细胞周期进程。尽管CD40L和抗Ig在早期的转录因子诱导相似，但在24小时时，表达的NF - κB和AP - 1核蛋白复合物存在细微差异。这种差异可能在决定通过这两种受体刺激对B细胞的不同影响方面发挥作用。
To address elements that might uniquely characterize CD40 mediated signaling, the nuclear expression of three transcription factors was evaluated following B cell stimulation by CD40L and by anti-lg antibody, Cross-linked CD40L was found to induce nuclear expression of NF-kappa B, AP-1 and NF-AT with a time course and intensity similar to that produced by anti-lg, Examination of NF-kappa B in more detail demonstrated that the CD40 mediated expression of DNA binding complexes correlated with induction of trans-activating activity which again attained similar levels following cross-linking of CD40 and slg, Despite the marked similarity in transcription factor induction triggered through CD40 and slg, differences in the intracellular signaling pathways utilized were apparent in that protein kinase C (PKC) depletion did not affect CD40 mediated induction of NF-kappa B even as induction by anti-lg was abolished, These results suggest that a 'final common pathway' or convergence of transcription factor induction may exist for two distinct receptors, each of which is individually capable of triggering cell cycle progression, despite the use of separate intracellular signaling pathways that differ at the level of PKC. Although transcription factor induction was similar for CD40L and anti-lg early on, subtle differences in expressed NF-kappa B and AP-1 nucleoprotein complexes were apparent at 24 h. Such differences may play a role in determining the variant effects on B cells of stimulation through these two receptors.