Phosphatases in concert with kinases set the gain for signal transduction through the T cell receptor.
Phosphatases in concert with kinases set the gain for signal transduction through the T cell receptor.
复制标题
磷酸酶与激酶协同作用，为通过 T 细胞受体的信号转导设定增益。
DOI：
10.1016/s0161-5890(03)00170-6
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发表时间：
2003
影响因子：
3.6
通讯作者：
Levine,AlanD
中科院分区：
文献类型：
--
作者：
Schade,AndrewE;Levine,AlanD
通过T细胞受体(TCR)/CD3信号复合体进行信号转导的“可调激活阈值”模型提出，磷酸化和去磷酸化的快速循环对于调节蛋白质-蛋白质相互作用的频率是不可或缺的，因此对下游信号通路的激活具有相当大的影响。同时激活激酶和磷酸酶可以调节正在进行的信号反应，这取决于它们对立的酶活性的相对平衡。虽然最近的报道已经解决了特定激酶/磷酸酶对促进信号传导的启动和终止的机制，但我们寻求对激酶/磷酸酶平衡调节或“调节”原代人T细胞中TCR信号传导的最接近步骤的能力有更全面的了解。在此，我们提供的生化证据表明，通过TCR诱导磷酸酪氨酸受到基于激酶和磷酸酶相对于彼此的总体活性的微调，导致磷酸化和去磷酸化的循环，这对开发下一代免疫治疗药物具有重要意义。
The ‘tunable activation thresholds’ model for signal transduction through the T cell receptor (TCR)/CD3 signaling complex proposes that rapid cycles of phosphorylation and dephosphorylation are integral to regulating the frequency of protein–protein interaction, thus having considerable influence over the activation of downstream signaling pathways. Co-temporal activation of kinases and phosphatases could serve to modulate the ongoing signaling response, depending on the relative balance of their opposing enzymatic activities. Although recent reports have addressed the mechanisms by which specific kinase/phosphatase pairs contribute to the initiation and termination of signaling, we sought a more global understanding of the ability of the kinase/phosphatase balance to regulate, or “tune”, the very proximal steps of TCR signaling in primary human T cells. Herein, we provide biochemical evidence that phosphotyrosine induction via the TCR is subject to fine-tuning based on the overall activity of kinases and phosphatases relative to one another, leading to cycles of phosphorylation and dephosphorylation, with implications for developing the next generation of immunotherapeutic agents.