A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling
A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling
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DOI：
10.1016/j.molcel.2007.06.015
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发表时间：
2007-08-03
期刊：
影响因子：
16
通讯作者：
Carpino, Nick
中科院分区：
文献类型：
--
作者：
Mikhailik, Anatoly;Ford, Bradley;Carpino, Nick
T细胞受体（TCR）的精确信号传导对于适当的免疫反应至关重要。为了确保T细胞对抗原刺激做出适当的反应，TCR信号传导途径受到多个水平的调节。Sts-1通过未知的机制负调节TCR下游的信号传导途径。在这里，我们证明Sts-1是一种磷酸酶，可以靶向酪氨酸激酶Zap-70等蛋白质。Sts-1 C末端的X射线结构显示，它与磷酸甘油酸酯/酸性磷酸酶（PGM/ AcP）家族的酶成员具有同源性，其中已知对PGM/AcP催化活性重要的残基在Sts-1中的性质和位置保守。在体外损害Sts-1磷酸酶活性的点突变也损害Sts-1调节T细胞中TCR信号传导的能力。这些观察结果揭示了参与抗原受体信号传导控制的PGM/ACP样酶活性。
Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The X-ray structure of the Sts-1 C terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/ AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling.