The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways.
The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways.
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DOI：
10.1016/j.molimm.2009.08.015
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发表时间：
2009-10
影响因子：
3.6
通讯作者：
Oh HW
中科院分区：
文献类型：
--
作者：
Carpino N;Chen Y;Nassar N;Oh HW
T细胞受体（TCR）检测感染性病原体的存在并激活许多细胞内信号传导途径。蛋白质酪氨酸磷酸化和泛素化作为TCR下游的关键调节机制。TCR信号传导途径的负调节在控制免疫应答中是重要的，并且TCR信号传导抑制蛋白（Sts-1和Sts-2）已显示作为TCR信号传导的关键负调节剂起作用。虽然它们的作用机制尚未完全揭示，但已知Sts蛋白具有内在的磷酸酶活性。在这里，我们证明，Sts-1和Sts-2是工具，在下调蛋白质，是双重修改的蛋白质酪氨酸磷酸化和泛素化。具体来说，来自缺乏Sts蛋白的基因工程小鼠的幼稚和活化T细胞在TCR刺激后显示出显著升高的酪氨酸磷酸化、泛素化蛋白水平。双重修饰的蛋白质的积累是短暂的，并且在活化的T细胞中而不是幼稚T细胞中通过共受体接合显著增强。我们的观察暗示了T细胞受体下游的一种新的调节机制。
The T cell receptor (TCR) detects the presence of infectious pathogens and activates numerous intracellular signaling pathways. Protein tyrosine phosphorylation and ubiquitination serve as key regulatory mechanisms downstream of the TCR. Negative regulation of TCR signaling pathways is important in controlling the immune response, and the Suppressor of TCR Signaling proteins (Sts-1 and Sts-2) have been shown to function as critical negative regulators of TCR signaling. Although their mechanism of action has yet to be fully uncovered, it is known that the Sts proteins possess intrinsic phosphatase activity. Here, we demonstrate that Sts-1 and Sts-2 are instrumental in down-modulating proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination. Specifically, both naïve and activated T cells derived from genetically engineered mice that lack the Sts proteins display strikingly elevated levels of tyrosine phosphorylated, ubiquitinated proteins following TCR stimulation. The accumulation of the dually modified proteins is transient, and in activated T cells but not naïve T cells is significantly enhanced by co-receptor engagement. Our observations hint at a novel regulatory mechanism downstream of the T cell receptor.
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