Rho family GTPases regulate VEGF-stimulated endothelial cell motility
Rho family GTPases regulate VEGF-stimulated endothelial cell motility
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DOI：
10.1006/excr.2001.5295
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发表时间：
2001-09-10
影响因子：
3.7
通讯作者：
Hruska, KA
中科院分区：
文献类型：
--
作者：
Soga, N;Namba, N;Hruska, KA
血管内皮生长因子（VEGF）诱导的内皮细胞迁移是血管生成的关键步骤。 VEGF 等生长因子刺激运动需要与细胞外基质 (ECM) 激活的信号转导途径相互作用。在这里，我们证明 Rac GTPase 是刺激内皮细胞运动过程中由 1 型胶原 ECM 和 VEGF 激活的关键交叉点。为了分析 Rho 家族 GTP 酶在 VEGF 刺激的内皮细胞趋化性和 ECM 刺激的趋触性中的作用，我们使用来自人类免疫缺陷病毒 Tat 蛋白的 Tat 肽在人包皮真皮内皮细胞中转导各自的融合蛋白。 VEGF 信号传导在趋化过程中需要 Rac 激活，而 Rac 和 Cdc42 在 I 型胶原的趋触过程中被激活。与 VEGF 类似，Rac 激活诱导内皮细胞应力纤维和粘着斑增加。令人惊讶的是，Rho 激活并不存在于胶原诱导的趋触性或 VEGF 的趋化性刺激中，尽管 Rho 诱导的应力纤维和粘着斑与 Rac 激活类似。 Rho 组成型激活的结果是趋触性受到抑制。因此，Rac 对于激活内皮细胞趋触性和 VEGF 刺激的趋化性是必需的且足够的。 (C) 2001 年学术出版社。
Migration of endothelial cells induced by vascular endothelial growth factor (VEGF) is a critical step in angiogenesis. Stimulation of motility by growth factors such as VEGF requires interaction with the signal transduction pathways activated by the extracellular matrix (ECM). Here we demonstrate that the Rac GTPase is the critical intersection activated by type 1 collagen ECM and VEGF during stimulation of endothelial cell motility. To analyze the role of the Rho family GTPases in VEGF-stimulated endothelial cell chemotaxis and ECM-stimulated haptotaxis, we transduced the respective fusion proteins in human foreskin dermal endothelial cells using a Tat peptide from the human immunodeficiency virus Tat protein. VEGF signaling required Rac activation during chemotaxis, and Rac and Cdc42 were activated during haptotaxis on type I collagen. Similar to VEGF, Rac activation induced an increase in endothelial cell stress fiber and focal adhesion. Surprisingly, Rho activation was not present in collagen-induced haptotaxis or stimulation of chemotaxis by VEGF, although Rho induced stress fibers and focal adhesions similar to Rac activation. The result of constitutive Rho activation was an inhibition of haptotaxis. Thus, Rac is required and sufficient for the activation of endothelial cell haptotaxis and VEGF-stimulated chemotaxis. (C) 2001 Academic Press.