Cutting Edge: Dok-1 and Dok-2 Adaptor Molecules Are Regulated by Phosphatidylinositol 5-Phosphate Production in T Cells
Cutting Edge: Dok-1 and Dok-2 Adaptor Molecules Are Regulated by Phosphatidylinositol 5-Phosphate Production in T Cells
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DOI：
10.4049/jimmunol.0804172
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Nunes, Jacques A.
中科院分区：
文献类型：
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作者：
Guittard, Geoffrey;Gerard, Audrey;Nunes, Jacques A.
酪氨酸激酶(DOK)下游蛋白DOK-1和DOK-2参与T细胞内稳态的维持。DOK蛋白酪氨酸磷酸化在T细胞信号负反馈环的建立中起着关键作用。这些结构上相关的接头分子包含一个Pleckstrin同源(PH)结构域，通常作为脂质/蛋白质相互作用模块。我们发现，这个PH结构域的存在对于DOK蛋白的酪氨酸磷酸化及其在T细胞中的负功能是必需的。我们发现DOK-1/DOK-2的PH结构域在体外与稀有的磷脂酰肌醇5-磷酸(PtdIns5P)结合。DOK酪氨酸磷酸化与TCR触发时T细胞中PtdIns5P的产生相关。此外，我们还证明了PtdIns5P的增加在体内调节了DOK酪氨酸的磷酸化。总之，我们的数据确定了T细胞信号转导中的一种新的脂质介质，并表明PH-PtdIns5P相互作用调节T细胞反应。免疫学杂志，2009,182：3974-3978。
Downstream of tyrosine kinase (Dok) proteins Dok-1 and Dok-2 are involved in T cell homeostasis maintenance. Dok protein tyrosine phosphorylation plays a key role in establishing negative feedback loops of T cell signaling. These structurally related adapter molecules contain a pleckstrin homology (PH) domain generally acting as a lipid/protein-interacting module. We show that the presence of this PH domain is necessary for the tyrosine phosphorylation of Dok proteins and their negative functions in T cells. We find that Dok-1/Dok-2 PH domains bind in vitro to the rare phosphoinositide species, phosphatidylinositol 5-phosphate (PtdIns5P). Dok tyrosine phosphorylation correlates with PtdIns5P production in T cells upon TCR triggering. Furthermore, we demonstrate that PtdIns5P increase regulates Dok tyrosine phosphorylation in vivo. Together, our data identify a novel lipid mediator in T cell signaling and suggest that PH-PtdIns5P interactions regulate T cell responses. The Journal of Immunology, 2009, 182: 3974-3978.