WASP recruitment to the T cell:APC contact site occurs independently of Cdc42 activation
WASP recruitment to the T cell:APC contact site occurs independently of Cdc42 activation
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DOI：
10.1016/s1074-7613(01)00178-9
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发表时间：
2001-08-01
期刊：
影响因子：
32.4
通讯作者：
Burkhardt, JK
中科院分区：
文献类型：
--
作者：
Cannon, JL;Labno, CM;Burkhardt, JK
Cdc42和WASP是肌动蛋白聚合的关键调节因子，其在T细胞信号传导中的功能尚不清楚。使用一种新的试剂，可以在固定细胞中特异性检测Cdc42- gtp，我们发现活化的Cdc42以抗原依赖的方式定位于T细胞：APC接触部位。仅TCR信号就足以诱导Cdc42-GTP的定位，并且需要功能性的Lck和Zap-70激酶。WASP也以抗原依赖的方式定位于T细胞：APC接触部位。令人惊讶的是，WASP定位与Cdc42结合域无关，但需要富含脯氨酸的结构域。我们的研究结果表明，WASP的局部激活需要多个信号的整合：WASP通过与含有SH3结构域的蛋白相互作用而被招募，并被集中在同一位点的Cdc42-GTP激活。
Cdc42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood. Using a novel reagent that specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42 localizes to the T cell:APC contact site in an antigen-dependent manner. TCR signaling alone was sufficient to induce localization of Cdc42-GTP, and functional Lck and Zap-70 kinases were required. WASP also localized to the T cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP localization was independent of the Cdc42 binding domain but required the proline-rich domain. Our results indicate that localized WASP activation requires the integration of multiple signals: WASP is recruited via interaction with SH3 domain-containing proteins and is activated by Cdc42-GTP concentrated at the same site.