Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK
Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK
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DOI：
10.1016/s1074-7613(03)00139-0
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发表时间：
2003-06-01
期刊：
影响因子：
32.4
通讯作者：
Kurosaki, T
中科院分区：
文献类型：
--
作者：
Johmura, S;Oh-hora, M;Kurosaki, T
尽管Vav家族蛋白对B细胞受体（BCR）信号传导很重要，但其激活机制仍知之甚少。我们在此证明，除了Vav之外，衔接分子Grb2和BLNK对于响应BCR刺激的有效Rac1激活也是必需的。Grb2或BLNK的缺失会导致Vav3向膜筏的转位减少。通过将Vav3表达为靶向膜筏的构建体，Grb2或BLNK缺陷型B细胞中缺陷的Rac1激活得以恢复。因此，我们的研究结果表明，Grb2和BLNK协同作用将Vav定位到膜筏中，从而有助于B细胞中Vav的最佳激活。
Despite the importance of the Vav family proteins for B cell receptor (BCR) signaling, their activation mechanisms remain poorly understood. We demonstrate here that adaptor molecules Grb2 and BLNK, in addition to Vav, are required for efficient Rac1 activation in response to BCR stimulation. Loss of either Grb2 or BLNK results in decreased translocation of Vav3 to membrane rafts. By expression of Vav3 as a raft-targeted construct, the defective Rac1 activation in Grb2- or BLNK-deficient B cells is restored. Hence, our findings suggest that Grb2 and BLNK cooperate to localize Vav into membrane rafts, thereby contributing to optimal activation of Vav in B cells.