Csk controls antigen receptor-mediated development and selection of T-lineage cells
Csk controls antigen receptor-mediated development and selection of T-lineage cells
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DOI：
10.1038/29802
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发表时间：
1998-08-27
期刊：
影响因子：
64.8
通讯作者：
Tarakhovsky, A
中科院分区：
文献类型：
--
作者：
Schmedt, C;Saijo, K;Tarakhovsky, A
α-βT淋巴细胞的发育和功能依赖于来自前T细胞和α-βT细胞受体(前TCR和α-βTCR)的信号(文献1，2)。这些受体的结合导致Lck和Fyn(3，4)的激活，这两个蛋白是Src家族的蛋白酪氨酸激酶(PTKs)。目前尚不清楚Src家族PTK的激活在多大程度上可以指导前TCR和αβTCR触发的分化步骤。在这里，我们表明，在未成熟的胸腺细胞中，Src家族PTKs的负调控因子，羧基末端Src激酶(CSK)(5)的失活，取消了对前TCR、αβTCR和主要组织相容性复合体(MHC)II类的需求，以发育成CD4(+)8(+)双阳性和CD4(+)单阳性胸腺细胞以及外周CD4αβT系细胞。这些数据表明，CSK及其底物需要建立前TCR/αβTCR介导的对αβT细胞发育的控制。
The development and function of alpha beta T lymphocytes depend on signals derived from pre-T and alpha beta T cell receptors (preTCR and alpha beta TCR) (reviewed in refs 1, 2). The engagement of these receptors leads to the activation of Lck and Fyn(3,4), which are protein tyrosine kinases (PTKs) of the Src family. It remains unclear to what extent the activation of Src-family PTKs can direct the differentiation steps triggered by preTCR and alpha beta TCR. Here we show that the inactivation of the negative regulator of Src-family PTKs, carboxy-terminal Src kinase (Csk)(5), in immature thymocytes abrogates the requirement for preTCR, alpha beta TCR and major histocompatibility complex (MHC) class II for the development of CD4(+)8(+) double-positive and CD4(+) single-positive thymocytes as well as peripheral CD4 alpha beta T-lineage cells. These data show that Csk and its substrates are required to establish preTCR/alpha beta TCR-mediated control over the development of alpha beta T cells.