T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1.

C Loh; J A Carew; J Kim; P G Hogan; A Rao

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T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1.

机译：T细胞受体刺激引起转录因子NFAT1的激活的早期和失活的后期。

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We show here that NFAT1 is rapidly activated, then slowly deactivated, by stimulation of T cells through their antigen receptor. Within minutes of T-cell receptor stimulation, NFAT1 is dephosphorylated, translocates from the cytoplasm into the nucleus, and shows an increase in its ability to bind to DNA. These changes are dependent on calcium mobilization and calcineurin activation, since they are also elicited by ionomycin and are blocked by the immunosuppressive drug cyclosporin A. After several hours of T-cell receptor stimulation, the majority of the NFAT1 in the cell reverts to its original phosphorylated form, reappears in the cytoplasm, and again displays a low affinity for DNA. Deactivation of NFAT1 is facilitated by phorbol 12-myristate 13-acetate and inhibitors of capacitative calcium entry and most likely reflects the slow return of intracellular free calcium concentrations towards resting levels. Our results suggest that calcineurin-dependent signalling pathways mediate the early activation of NFAT1, while phorbol 12-myristate 13-acetate-dependent feedback pathways contribute to the late deactivation. Persistent NFAT-dependent cytokine gene transcription in activated T cells may be mediated by other NFAT family proteins in addition to NFAT1 during the immune response.

机译：我们在这里显示NFAT1通过刺激T细胞通过其抗原受体而被快速激活，然后缓慢失活。在T细胞受体刺激的几分钟内，NFAT1被去磷酸化，从细胞质移入细胞核，并显示出与DNA结合的能力增强。这些变化取决于钙动员和钙调神经磷酸酶的激活，因为它们也被离子霉素诱导并被免疫抑制药物环孢菌素A阻断。在T细胞受体刺激数小时后，细胞中的大多数NFAT1恢复为原始状态磷酸化的形式，重新出现在细胞质中，并再次显示对DNA的低亲和力。佛波醇12-肉豆蔻酸酯13-乙酸酯和电容性钙进入抑制剂可促进NFAT1的失活，这很可能反映了细胞内游离钙浓度缓慢恢复到静息水平。我们的结果表明，钙调磷酸酶依赖性信号通路介导NFAT1的早期激活，而佛波醇12-肉豆蔻酸酯13-乙酸酯依赖性反馈通路则有助于晚期失活。在免疫应答过程中，除NFAT1外，活化的T细胞中持久性NFAT依赖性细胞因子基因的转录还可能由其他NFAT家族蛋白介导。

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《Molecular and Cellular Biology》 |1996年第7期|共10页
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C Loh; J A Carew; J Kim; P G Hogan; A Rao;
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中图分类细胞生物学;
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6. T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1. [O] . C Loh, J A Carew, J Kim, 1996

机译：T细胞受体刺激引起转录因子NFAT1的激活的早期和失活的后期。
7. T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1. [O] . Loh, C, Carew, J A, Kim, J, 1996

机译：T细胞受体刺激引起转录因子NFAT1的激活的早期和失活的后期。

T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1.

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