IDENTIFICATION OF A PUTATIVE REGULATOR OF EARLY T-CELL ACTIVATION GENES
IDENTIFICATION OF A PUTATIVE REGULATOR OF EARLY T-CELL ACTIVATION GENES
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DOI：
10.1126/science.3260404
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发表时间：
1988-07-08
期刊：
影响因子：
56.9
通讯作者：
CRABTREE, GR
中科院分区：
文献类型：
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作者：
SHAW, JP;UTZ, PJ;CRABTREE, GR
利用T细胞激活特异性白介素2增强子(IL-2)的功能序列，研究了早期T细胞激活基因的抗原受体依赖性调控分子。其中一个序列与活化T细胞的核提取物形成蛋白质复合体NFAT-1。这种复合体在IL-2基因激活前10到25分钟出现。对蛋白质合成抑制剂的研究表明，Jurkat T细胞中IL-2基因激活物的合成时间与NFAT-1的出现时间相对应。NFAT-1，或非常类似的蛋白质，是人类免疫缺陷病毒1型的长末端重复序列的结合功能序列；这种病毒的长末端重复序列已知在T细胞早期激活时被刺激。该复合体的结合部位在转染抗原受体激活的T细胞后激活了一个连接的启动子，但不能激活其他类型的细胞。这些特征表明，NFAT-1传递的信号起始于T细胞抗原受体。
Molecules involved in the antigen receptor-dependent regulation of early T cell activation genes were investigated with the use of functional sequences of the T cell activation-specific enhancer of interleukin-2 (IL-2). One of these sequences forms a protein complex, NFAT-1, specifically with nuclear extracts of activated T cells. This complex appeared 10 to 25 minutes before the activation of the IL-2 gene. Studies with inhibitors of protein synthesis indicated that the time of synthesis of the activator of the IL-2 gene in Jurkat T cells corresponds to the time of appearance of NFAT-1. NFAT-1, or a very similar protein, bound functional sequences of the long terminal repeat (LTR) of the human immunodeficiency virus type 1; the LTR of this virus is known to be stimulated during early T cell activation. The binding site for this complex activated a linked promoter after transfection into antigen receptor-activated T cells but not other cell types. These characteristics suggest that NFAT-1 transmits signals initiated at the T cell antigen receptor.