Schmedt C, Saijo K, Niidome T, Kühn R, Aizawa S, Tarakhovsky A
Laboratory for Lymphocyte Signalling, University of Cologne, Germany.
Nature. 1998 Aug 27;394(6696):901-4. doi: 10.1038/29802.
The development and function of alphabetaT lymphocytes depend on signals derived from pre-T and alphabetaT cell receptors (preTCR and alphabetaTCR) (reviewed in refs 1, 2). The engagement of these receptors leads to the activation of Lck and Fyn, 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 alphabetaTCR. Here we show that the inactivation of the negative regulator of Src-family PTKs, carboxy-terminal Src kinase (Csk), in immature thymocytes abrogates the requirement for preTCR, alphabetaTCR 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 alphabetaT-lineage cells. These data show that Csk and its substrates are required to establish preTCR/alphabetaTCR-mediated control over the development of alphabetaT cells.
αβT淋巴细胞的发育和功能取决于源自前T细胞和αβT细胞受体（前TCR和αβTCR）的信号（参考文献1、2中有相关综述）。这些受体的结合会导致Lck和Fyn的激活，它们是Src家族的蛋白酪氨酸激酶（PTK）。目前尚不清楚Src家族PTK的激活在多大程度上能够指导由前TCR和αβTCR触发的分化步骤。在此我们表明，未成熟胸腺细胞中Src家族PTK的负调节因子羧基末端Src激酶（Csk）的失活消除了前TCR、αβTCR和主要组织相容性复合体（MHC）II类对于CD4+8+双阳性和CD4+单阳性胸腺细胞以及外周CD4αβT谱系细胞发育的需求。这些数据表明，Csk及其底物对于建立前TCR/αβTCR介导的对αβT细胞发育的控制是必需的。
