The role of diacylglycerol kinases in T cell anergy.

X P Zhong, B A Olenchock, G A Koretzky
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Abstract

Engagement of the T cell antigen receptor (TCR) results in the activation of multiple biochemical second messenger cascades that must be integrated for the appropriate T cell response. Once the critical TCR-stimulated signaling pathway is initiated by activation of protein tyrosine kinases, a series of adapter proteins is recruited that brings tyrosine-phosphorylated phospholipase Cgamma1 into the vicinity of its substrate, phosphatidylinositol-4,5-bisphosphate, resulting in the formation of two second messengers, inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Previous work from multiple laboratories has shown that the balance between signals downstream of IP3 versus those downstream of DAG has profound effects on the fate of the stimulated T cells. In this report we summarize our recent data indicating that one key determinant of this balance of signals is the activity of members of the diacylglycerol kinase family, enzymes that convert DAG into phosphatidic acid.

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二酰甘油激酶在T细胞能量中的作用。
T细胞抗原受体(TCR)的参与导致多个生化第二信使级联的激活,这些级联必须整合以实现适当的T细胞反应。一旦酪氨酸激酶激活了tcr刺激的关键信号通路,就会招募一系列适配器蛋白,将酪氨酸磷酸化的磷脂酶Cgamma1带到其底物磷脂酰肌醇4,5-二磷酸附近,从而形成两个第二信使,肌醇1,4,5-三磷酸(IP3)和二酰基甘油(DAG)。先前来自多个实验室的研究表明,IP3下游信号与DAG下游信号之间的平衡对受刺激T细胞的命运有着深远的影响。在这篇报告中,我们总结了我们最近的数据,表明信号平衡的一个关键决定因素是二酰基甘油激酶家族成员的活性,这些酶将DAG转化为磷脂酸。
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