POLKADOTS are foci of functional interactions in T-cell receptor-mediated signaling to NF-κB
POLKADOTS are foci of functional interactions in T-cell receptor-mediated signaling to NF-κB
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DOI：
10.1091/mbc.e05-10-0985
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Schaefer, BC
中科院分区：
文献类型：
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作者：
Rossman, JS;Stoicheva, NG;Schaefer, BC
T细胞受体（TCR）的刺激导致包括NF-κ B在内的几种转录因子的激活，这些转录因子对于T细胞增殖和效应子功能的获得至关重要。在TCR参与时，TCR指导的NF-κ B信号通路内的几种蛋白质经历动态空间再分布，但这些再分布事件的意义在很大程度上是未知的。我们先前描述了TCR诱导的称为POLKADOTS（点状和寡聚体杀伤或激活结构域转导信号）的胞质结构，其富含NF-κ B信号传导中间体Bcl 10。我们现在表明，这些结构的形成条件下，促进有效的NF-κ B激活。此外，POLKADOTS的形成依赖于特定NF-κ B信号转导子的功能结构域。通过使用光活化的GFP，我们证明POLKADOTS含有高度稳定和快速平衡的蛋白质组分。FRET分析表明，POLKADOTS是Bcl 10和伴侣信号蛋白之间富集相互作用的位点。这些观察结果有力地表明，POLKADOTS是NF-κ B的TCR活化过程中胞质中间体之间动态信息交换的焦点位点。
Stimulation of the T-cell receptor (TCR) results in the activation of several transcription factors, including NF-kappa B, that are crucial for T-cell proliferation and gain of effector functions. On TCR engagement, several proteins within the TCR-directed NF-kappa B signaling pathway undergo dynamic spatial redistribution, but the significance of these redistribution events is largely unknown. We have previously described TCR-induced cytoplasmic structures called POLKADOTS (punctate and oligomeric killing or activating domains transducing signals) that are enriched in the NF-kappa B signaling intermediate, Bcl10. We now show that these structures are formed only under conditions that promote efficient NF-kappa B activation. Furthermore, POLKADOTS formation is dependent on functional domains of specific NF-kappa B signal transducers. Through use of a photoactivatable GFP, we demonstrate that POLKADOTS contain both a highly stable and a rapidly equilibrating protein component. FRET analyses show that POLKADOTS are sites of enriched interactions between Bcl10 and partner signaling proteins. These observations strongly suggest that POLKADOTS are focal sites of dynamic information exchange between cytosolic intermediates in the process of TCR activation of NF-kappa B.