The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1.
The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1.
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DOI：
10.1083/jcb.200801121
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发表时间：
2008-09-22
期刊：
影响因子：
--
通讯作者：
Billadeau DD
中科院分区：
文献类型：
--
作者：
Nolz JC;Nacusi LP;Segovis CM;Medeiros RB;Mitchell JS;Shimizu Y;Billadeau DD
WAVE 2调节T细胞受体（TCR）刺激的肌动蛋白细胞骨架动力学，导致整合素聚集和亲和力成熟。虽然WAVE 2介导的整合素亲和力成熟招募纽蛋白和talin的免疫突触Arp 2/3依赖性的方式，它调节整合素集群的机制尚不清楚。我们发现，Abl酪氨酸激酶与WAVE 2复合物和TCR连接诱导WAVE 2依赖性膜募集的TGFR 1。此外，我们发现，WAVE 2调节TCR介导的激活整合素调节鸟苷三磷酸酶Rap 1通过招募和激活的CrkL-C3 G交换复合物。此外，我们证明，虽然Abl不调节CrkL-C3 G进入膜的招聘，它确实影响C3 G的酪氨酸磷酸化，这是必需的鸟嘌呤核苷酸交换因子对Rap 1的活性。该信号传导节点不仅调节TCR刺激的整合素聚集，而且调节亲和力成熟。这些发现确定了一种以前未知的机制，WAVE 2复合物通过该机制调节TCR信号转导至Rap 1和整合素活化。
WAVE2 regulates T cell receptor (TCR)–stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL–C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL–C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation.
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影响因子：
20.3
作者：
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