PROTEIN-TYROSINE KINASE P56(LCK) CONTROLS ALLELIC EXCLUSION OF T-CELL RECEPTOR BETA-CHAIN GENES
PROTEIN-TYROSINE KINASE P56(LCK) CONTROLS ALLELIC EXCLUSION OF T-CELL RECEPTOR BETA-CHAIN GENES
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DOI：
10.1038/365552a0
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发表时间：
1993-10-07
期刊：
影响因子：
64.8
通讯作者：
PERLMUTTER, RM
中科院分区：
文献类型：
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作者：
ANDERSON, SJ;LEVIN, SD;PERLMUTTER, RM
在 T 细胞发育过程中，介导 T 细胞受体 (TCR) β 链和 α 链基因组装的位点特异性 DNA 重排是按发育顺序排列的 1,2。特别是，完整 β 链基因的组装和表达会阻止 β 基因座的进一步重排（这一过程称为等位基因排除）3 并驱动 CD4+8+ 细胞的生成和扩增 4,5。尽管 TCRbeta 链传递此类信号的机制尚不清楚，但对转基因动物的研究表明，淋巴细胞特异性蛋白酪氨酸激酶 p56lck 可能会影响类似的信号传导途径6。 TCRbeta 链通过 p56lck 传递细胞内信号的假设做出了明确的预测：干扰 p56lck 功能将减轻同时表达的 TCRbeta 链的影响。在这里，我们通过检查表达功能性 TCRbeta 链转基因和催化失活形式的 p56lck 的小鼠的等位基因排除来证实这一预测。
DURING T-cell development, site-specific DNA rearrangements mediating assembly of beta- and alpha-chain genes of the T-cell receptor (TCR) are developmentally ordered1,2. In particular, assembly and expression of a complete beta-chain gene blocks further rearrangements at the beta-locus (a process referred to as allelic exclusion)3 and drives the generation and expansion of CD4+8+ cells4,5. Although the mechanism used by TCRbeta chains to deliver such signals is unknown, studies in transgenic animals have suggested that the lymphocyte-specific protein tyrosine kinase p56lck may impinge on a similar signalling pathway6. The hypothesis that TCRbeta chains deliver intracellular signals via p56lck makes an explicit prediction: that interference with p56lck function will mitigate the effects of a simultaneously expressed TCRbeta chain. Here we confirm this prediction through examination of allelic exclusion in mice expressing both a functional TCRbeta chain transgene and a catalytically inactive form of p56lck.