Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-κB and NFAT

Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-κB and NFAT
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DOI:
10.1038/87704
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发表时间:
2001-05-01
期刊:
影响因子:
30.5
通讯作者:
von Boehmer, H
von Boehmer, H
中科院分区:
医学1区
文献类型:
--
作者:
Aifantis, I;Gounari, F;von Boehmer, H

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前T细胞抗原受体(Pre-TCR)信号在未成熟T细胞的发育过程中起着至关重要的作用,尽管近端Pre-TCR信号的某些方面已经被研究过,但对中间信号转导和远端转录调节因子的研究还很少。我们在此报告了TCR前信号与胞浆钙离子浓度双相升高之间的相关性。此外,我们还证明了结构性的Pre-TCR信号与通过储藏操作的质膜Ca~(2+)通道的Ca~(2+)内流速率的增加有关,我们还证明了Pre-TCR诱导的胞浆Ca~(2+)升高的双相性对发育中的T细胞中转录因子NF-kappaB和NFAT的活性进行了差异调节。
Pre-T cell antigen receptor (pre-TCR) signaling plays a crucial role in the development of immature T cells,Although certain aspects of proximal pre-TCR signaling have been studied, the intermediate signal transducers and the distal transcription modulators have been poorly characterized. We report here a correlation between pre-TCR signaling and a biphasic rise in the cytosolic Ca2+ concentration. In addition, we show that constitutive pre-TCR signaling is associated with an increased rate of Ca2+ influx through store-operated plasma membrane Ca2+ channels,We show also that the biphasic nature of the observed pre-TCR-induced rise in cytosolic Ca2+ differentially modulates the activities of the transcription factors NF-kappaB and NFAT in developing T cells.