DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, in T cells
DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, in T cells
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DOI：
10.1016/s1074-7613(03)00169-9
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发表时间：
2003-07-01
期刊：
影响因子：
32.4
通讯作者：
Fukui, Y
中科院分区：
文献类型：
--
作者：
Sanui, T;Inayoshi, A;Fukui, Y
DOCK2是秀丽隐杆线虫CED-5和果蝇成肌细胞城的哺乳动物同源物，它们调节肌动蛋白细胞骨架。DOCK2对淋巴细胞迁移至关重要，但DOCK2在TCR信号转导中的作用尚不清楚。我们证明DOCK2在TCR介导的RAC激活和免疫突触形成中是必不可少的。在DOCK2缺陷的T细胞中，抗原诱导的TCR和脂筏移位到APC界面的功能严重受损，导致抗原特异性T细胞的增殖显著降低。此外，我们还发现DOCK2基因缺陷小鼠的正选择和负选择的效果都降低了。这些结果表明，DOCK2通过激活RAC重塑肌动蛋白细胞骨架来调节T细胞的反应性。
DOCK2 is a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City which are known to regulate actin cytoskeleton. DOCK2 is critical for lymphocyte migration, yet the role of DOCK2 in TCR signaling remains unclear. We show here that DOCK2 is essential for TCR-mediated Rac activation and immunological synapse formation. In DOCK2-deficient T cells, antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, to the APC interface was severely impaired, resulting in a significant reduction of antigen-specific T cell proliferation. In addition, we found that the efficacy of both positive and negative selection was reduced in DOCK2-deficient mice. These results suggest that DOCK2 regulates T cell responsiveness through remodeling of actin cytoskeleton via Rac activation.