Lavenburg Kim R, Ivey Jennifer, Hsu Tien, Muise-Helmericks Robin C
Laboratory of Cancer Genomics, Hollings Cancer Center, and Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston 29425, USA.
FASEB J. 2003 Dec;17(15):2278-80. doi: 10.1096/fj.03-0040fje. Epub 2003 Oct 2.
We investigated the inter-relationship between two downstream effectors of vascular endothelial growth factor (VEGF), the serine threonine kinase Akt (also known as protein kinase B) and the transcription factor ETS1, during tubulogenesis. Human endothelial cell culture and the in vivo Drosophila tracheal systems are employed in comparative analysis. We show that VEGF stimulates the expression of ETS1 through a phosphatidylinositol-3-kinase (PI3K)/Akt-dependent pathway in primary endothelial cells. Activation of Akt results in vessel formation in vitro, a process that is blocked by expression of antisense ETS1. The functional relationship between ETS and Akt was then tested in the homologous tubular system in Drosophila. Contrary to expectation, ETS1 and Akt did not form a linear positive regulatory pathway in vivo. Instead, genetic analyses suggest that the Drosophila ETS1 homologue Pointed is required for cell motility per se while Drosophila Akt (Dakt1) is responsible for organized and restricted cell movement that is essential for tubule formation. Taken together, our results show that ETS1 and Akt control different aspects of cell motility that are integrated in the precise regulation of vascular tubule formation.
我们研究了血管内皮生长因子（VEGF）的两个下游效应器——丝氨酸苏氨酸激酶Akt（也称为蛋白激酶B）和转录因子ETS1在血管生成过程中的相互关系。采用人内皮细胞培养和体内果蝇气管系统进行比较分析。我们发现，VEGF通过磷脂酰肌醇-3-激酶（PI3K）/Akt依赖性途径刺激原代内皮细胞中ETS1的表达。Akt的激活导致体外血管形成，这一过程被反义ETS1的表达所阻断。然后在果蝇的同源管状系统中测试了ETS和Akt之间的功能关系。与预期相反，ETS1和Akt在体内并未形成线性正调控途径。相反，遗传分析表明，果蝇ETS1的同源物Pointed本身是细胞运动所必需的，而果蝇Akt（Dakt1）则负责有组织且受限的细胞运动，这对小管形成至关重要。综上所述，我们的结果表明，ETS1和Akt控制细胞运动的不同方面，这些方面在血管小管形成的精确调控中相互整合。
