Regulation of VeGF-mediated angiogenesis by the Akt/PKB substrate Girdin
Regulation of VeGF-mediated angiogenesis by the Akt/PKB substrate Girdin
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DOI：
10.1038/ncb1695
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发表时间：
2008-03-01
影响因子：
21.3
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Kitamura, Tomoya;Asai, Naoya;Takahashi, Masahide
丝氨酸/苏氨酸蛋白激酶Akt参与多种细胞过程，包括细胞增殖、存活、代谢和基因表达。它是血管内皮生长因子（VEGF）介导的血管生成所必需的；然而，Akt如何调节内皮细胞的迁移，这是血管新生过程中血管发芽、分支和网络形成的关键过程，目前尚不清楚。在这里，我们报道了akt介导的Girdin磷酸化，一种肌动蛋白结合蛋白，促进内皮细胞依赖vegf的迁移和这些细胞的管形成。我们发现外源性携带有Girdin短干扰RNA的腺病毒嵌入小鼠体内，可以显著抑制vegf介导的血管生成。在小鼠中靶向破坏Girdin基因会损害视网膜血管重构和主动脉环血管生成，而Girdin对于胚胎血管生成是必不可少的。这些发现表明Akt/Girdin信号通路在vegf介导的新生儿血管生成中起重要作用。
The serine/threonine protein kinase Akt is involved in a variety of cellular processes including cell proliferation, survival, metabolism and gene expression. It is essential in vascular endothelial growth factor (VEGF)-mediated angiogenesis; however, it is not known how Akt regulates the migration of endothelial cells, a crucial process for vessel sprouting, branching and the formation of networks during angiogenesis. Here we report that Akt-mediated phosphorylation of Girdin, an actin-binding protein, promotes VEGF-dependent migration of endothelial cells and tube formation by these cells. We found that exogenously delivered adenovirus harbouring Girdin short interfering RNA in Matrigel embedded in mice, markedly inhibited VEGF-mediated angiogenesis. Targeted disruption of the Girdin gene in mice impaired vessel remodelling in the retina and angiogenesis from aortic rings, whereas Girdin was dispensable for embryonic vasculogenesis. These findings demonstrate that the Akt/Girdin signalling pathway is essential in VEGF-mediated postneonatal angiogenesis.