Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2
Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2
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DOI：
10.1016/s1074-7613(03)00351-0
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发表时间：
2004-01-01
期刊：
影响因子：
32.4
通讯作者：
Ihle, JN
中科院分区：
文献类型：
--
作者：
Carpino, N;Turner, S;Ihle, JN
T细胞在识别和消除外来病原体方面发挥着核心作用。通过T细胞受体（TCR）的信号控制T细胞应答的程度和持续时间。为了确保T细胞不会被不适当地激活，TCR下游的信号传导途径受到多个水平的正调控和负调控。在这里，我们描述了两个相关的蛋白质，Sts-1和Sts-2，负调控TCR信号。来自缺乏Sts-1和Sts-2的小鼠的T细胞对TCR刺激反应过度。该表型伴随着增加的Zap-70磷酸化和活化，包括其泛素化形式。此外，在多发性硬化症的小鼠模型中观察到TCR下游的信号蛋白的超活化、Sts 1/2（-/-）T细胞的细胞因子产生的显著增加以及对自身免疫的易感性增加。因此，Sts-1和Sts-2是调节T细胞活化的信号通路的关键调节剂。
T cells play a central role in the recognition and elimination of foreign pathogens. Signals through the T cell receptor (TCR) control the extent and duration of the T cell response. To ensure that T cells are not inappropriately activated, signaling pathways downstream of the TCR are subject to multiple levels of positive and negative regulation. Herein, we describe two related proteins, Sts-1 and Sts-2, that negatively regulate TCR signaling. T cells from mice lacking Sts-1 and Sts-2 are hyperresponsive to TCR stimulation. The phenotype is accompanied by increased Zap-70 phosphorylation and activation, including its ubiquitinylated forms. Additionally, hyperactivation of signaling proteins downstream of the TCR, a marked increase in cytokine production by Sts1/2(-/-) T cells, and increased susceptibility to autoimmunity in a mouse model of multiple sclerosis is observed. Therefore, Sts-1 and Sts-2 are critical regulators of the signaling pathways that regulate T cell activation.