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首页> 外文期刊>Molecular and Cellular Biology >RIAM Links the ADAP/SKAP-55 Signaling Module to Rap1, Facilitating T-Cell-Receptor-Mediated Integrin Activation
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RIAM Links the ADAP/SKAP-55 Signaling Module to Rap1, Facilitating T-Cell-Receptor-Mediated Integrin Activation

机译：RIAM将ADAP / SKAP-55信号模块链接到Rap1，从而促进T细胞受体介导的整合素激活

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摘要

One outcome of T-cell receptor (TCR) signaling is increased affinity and avidity of integrins for their ligands. This occurs through a process known as inside-out signaling, which has been shown to require several molecular components including the adapter proteins ADAP (adhesion and degranulation-promoting adapter protein) and SKAP-55 (55-kDa src kinase-associated phosphoprotein) and the small GTPase Rap1. Herein, we provide evidence linking ADAP and SKAP-55 to RIAM, a recently described adapter protein that binds selectively to active Rap1. We identified RIAM as a key component linking the ADAP/SKAP-55 module to the small GTPase Rap1, facilitating TCR-mediated integrin activation. We show that RIAM constitutively interacts with SKAP-55 in both a heterologous transfection system and primary T cells and map the region essential for this interaction. Additionally, we find that the SKAP-55/RIAM complex is essential both for TCR-mediated adhesion and for efficient conjugate formation between T cells and antigen-presenting cells. Mechanistic studies revealed that the ADAP/SKAP-55 module relocalized RIAM and Rap1 to the plasma membrane following TCR activation to facilitate integrin activation. These results describe for the first time a link between ADAP/SKAP-55 and the Rap1/RIAM complex and provide a potential new mechanism for TCR-mediated integrin activation.
机译：T细胞受体（TCR）信号转导的一种结果是整合素对其配体的亲和力和亲合力增加。这是通过一种由内而外的信号传导过程发生的，该过程已显示需要多种分子成分，包括衔接蛋白ADAP（促进粘附和脱粒的衔接蛋白）和SKAP-55（55-kDa src激酶相关的磷酸化蛋白）和小的GTPase Rap1。在本文中，我们提供了将ADAP和SKAP-55与RIAM（最近描述的选择性结合活性Rap1的衔接子蛋白）相关的证据。我们确定了RIAM是将ADAP / SKAP-55模块连接到小型GTPase Rap1的关键组件，从而促进了TCR介导的整联蛋白激活。我们显示，RIAM与SKAP-55在异源转染系统和原代T细胞中组成性相互作用，并绘制该相互作用必不可少的区域。此外，我们发现SKAP-55 / RIAM复合物对于TCR介导的粘附以及T细胞与抗原呈递细胞之间有效的偶联物形成都是必不可少的。机理研究表明，TCR激活后，ADAP / SKAP-55模块将RIAM和Rap1重新定位到质膜上，以促进整联蛋白激活。这些结果首次描述了ADAP / SKAP-55与Rap1 / RIAM复合物之间的联系，并为TCR介导的整联蛋白激活提供了潜在的新机制。

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