The dynamic distribution of CARD11 at the immunological synapse is regulated by the inhibitory kinesin GAKIN.

The dynamic distribution of CARD11 at the immunological synapse is regulated by the inhibitory kinesin GAKIN.
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DOI:
10.1016/j.molcel.2010.11.007
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发表时间:
2010-12-10
期刊:
影响因子:
16
通讯作者:
Pomerantz JL
Pomerantz JL
中科院分区:
生物学1区
文献类型:
--
作者:
Lamason RL;Kupfer A;Pomerantz JL

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T细胞受体(TcR)是抗原诱导的T细胞活化所必需的信号转导至核因子-κB。我们对CARD11的修饰物进行了表达克隆筛选,并鉴定了Kinesin-3家族成员Gakin是CARD11的抑制因子。Gakin负性调节转录因子受体信号,以信号依赖的方式与κ结合,并能与所需的信号蛋白Bcl10竞争结合。此外,Gakin动态地定位于免疫突触,并调节CARD11从突触中央区域到远端区域的重新分布。我们认为CARD11支架的功能和在突触中心的占有率受到Gakin的负调控,以调节抗原-受体信号的输出。
T cell receptor (TCR) signaling to NF-κB is required for antigen-induced T cell activation. We conducted an expression-cloning screen for modifiers of CARD11, a critical adapter in antigen-receptor signaling, and identified the kinesin-3 family member GAKIN as a CARD11 inhibitor. GAKIN negatively regulates TCR signaling to NF-κB, associates with CARD11 in a signal-dependent manner, and can compete with the required signaling protein, Bcl10, for association. In addition, GAKIN dynamically localizes to the immunological synapse and regulates the redistribution of CARD11 from the central region of the synapse to a distal region. We propose that CARD11 scaffold function and occupancy at the center of the synapse are negatively regulated by GAKIN to tune the output of antigen-receptor signaling.
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