Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mol Cell. 2010 Dec 10;40(5):798-809. doi: 10.1016/j.molcel.2010.11.007.
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 adaptor 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.
T 细胞受体 (TCR) 向 NF-κB 的信号转导对于抗原诱导的 T 细胞激活是必需的。我们进行了一项表达克隆筛选，以寻找抗原受体信号转导中关键衔接蛋白 CARD11 的调节剂，发现驱动蛋白-3 家族成员 GAKIN 是 CARD11 的抑制剂。GAKIN 负调控 TCR 向 NF-κB 的信号转导，以信号依赖的方式与 CARD11 相关联，并可以与所需的信号蛋白 Bcl10 竞争结合。此外，GAKIN 动态定位到免疫突触，并调节 CARD11 从突触的中心区域向远端区域的重新分布。我们提出，GAKIN 负调控 CARD11 支架功能和在突触中心的占据，以调节抗原受体信号转导的输出。
