Functional Cooperation between the Proteins Nck and ADAP Is Fundamental for Actin Reorganization
Functional Cooperation between the Proteins Nck and ADAP Is Fundamental for Actin Reorganization
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DOI：
10.1128/mcb.01358-10
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发表时间：
2011-07-01
影响因子：
5.3
通讯作者：
Barda-Saad, Mira
中科院分区：
文献类型：
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作者：
Pauker, Maor H.;Reicher, Barak;Barda-Saad, Mira
T细胞抗原受体（TCR）激活触发肌动蛋白细胞骨架的深刻变化。除了控制细胞的形状和极性，这个过程还调节重要的T细胞反应，如T细胞粘附，运动和增殖。这些依赖于信号传导蛋白Nck和Wiskott-Aldrich综合征蛋白（WASp）向TCR活化位点的募集以及用于活化T细胞的衔接蛋白接头（LAT）和76 kDa的含SH 2结构域的白细胞蛋白（SLP 76）的功能特性。我们现在证明，Nck是必要的，但不足以招募WASp。我们发现，两种途径导致SLP 76依赖的肌动蛋白重排。一个需要SLP 76酸性结构域，这对与Nck SH 2结构域的结合至关重要，另一个需要SLP 76 SH 2结构域，这对与促进粘附和脱颗粒的衔接蛋白ADAP的相互作用至关重要。Nck和ADAP之间的功能合作介导SLP 76-WASp相互作用和肌动蛋白重排。我们还揭示了连接ADAP肌动蛋白重组的分子机制。
T cell antigen receptor (TCR) activation triggers profound changes in the actin cytoskeleton. In addition to controlling cellular shape and polarity, this process regulates vital T cell responses, such as T cell adhesion, motility, and proliferation. These depend on the recruitment of the signaling proteins Nck and Wiskott-Aldrich syndrome protein (WASp) to the site of TCR activation and on the functional properties of the adapter proteins linker for activation of T cells (LAT) and SH2-domain-containing leukocyte protein of 76 kDa (SLP76). We now demonstrate that Nck is necessary but insufficient for the recruitment of WASp. We show that two pathways lead to SLP76-dependent actin rearrangement. One requires the SLP76 acidic domain, crucial to association with the Nck SH2 domain, and another requires the SLP76 SH2 domain, essential for interaction with the adhesion- and degranulation-promoting adapter protein ADAP. Functional cooperation between Nck and ADAP mediates SLP76-WASp interactions and actin rearrangement. We also reveal the molecular mechanism linking ADAP to actin reorganization.