Vav GEFs regulate macrophage morphology and adhesion-induced Rac and Rho activation
Vav GEFs regulate macrophage morphology and adhesion-induced Rac and Rho activation
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DOI：
10.1016/j.yexcr.2009.08.010
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发表时间：
2009-11-15
影响因子：
3.7
通讯作者：
Ridley, Anne J.
中科院分区：
文献类型：
--
作者：
Bhavsar, Parag J.;Vigorito, Elena;Ridley, Anne J.
Vav 蛋白家族有可能充当 Rho GTPases 的信号转导适配器和 GEF。因此，它们被提议作为各种细胞类型中细胞骨架的调节剂。我们使用缺乏所有三种 Vav 亚型的小鼠的巨噬细胞来确定它们的功能如何影响细胞形态和迁移。缺乏Vav蛋白的巨噬细胞采用所有细长的形态并且在培养物中具有增强的迁移持久性。为了研究 Vav 蛋白发挥作用的途径，我们分析了巨噬细胞对趋化剂 CSF-1 和粘附的反应。我们发现巨噬细胞对 CSF-1 的形态和信号反应不需要 Vav 蛋白。相比之下，粘附诱导的细胞扩散、RhoA 和 Rac1 激活以及细胞信号传导均依赖于油 Vav 蛋白。我们提出 Vav 蛋白通过将粘附受体与 Rac1 和 RhoA 活性偶联并通过充当接头来调节粘附信号事件（例如桩蛋白和 ERK1/2 磷酸化）来影响巨噬细胞形态和运动行为。 (C) 2009 Elsevier Inc. 保留所有权利。
The Vav family of proteins have the potential to act as both signalling adapters and GEFs for Rho GTPases. They have therefore been proposed as regulators of the cytoskeleton in various cell types. We have used macrophages from mice deficient in all three Vav isoforms to determine how their function affects cell morphology and migration. Macrophages lacking Vav proteins adopt ail elongated morphology and have enhanced migratory persistence in culture. To investigate the pathways through which Vav proteins exert their effects we analysed the responses of macrophages to the chemoattractant CSF-1 and to adhesion. We found that morphological and signalling responses of macrophages to CSF-1 did not require Vav Proteins. In contrast, adhesion-induced cell spreading, RhoA and Rac1 activation and cell signalling were all dependent oil Vav proteins. We Propose that Vav Proteins affect macrophage Morphology and motile behaviour by coupling adhesion receptors to Rac1 and RhoA activity and regulating adhesion signalling events such as paxillin and ERK1/2 phosphorylation by acting as adapters. (C) 2009 Elsevier Inc. All rights reserved.