VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide synthase, and caveolin-1 in vascular endothelial cells
VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide synthase, and caveolin-1 in vascular endothelial cells
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DOI：
10.1006/bbrc.1998.9790
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发表时间：
1999-03-05
影响因子：
3.1
通讯作者：
Caldwell, RB
中科院分区：
文献类型：
--
作者：
Feng, YY;Venema, VJ;Caldwell, RB
VEGF 通过需要 NOS 活性的过程增加内皮细胞通透性和生长。由于 eNOS 活性是通过其与小凹结构蛋白 Caveolin-1 的相互作用来调节的，因此我们分析了 VEGF 对 eNOS、caveolin-1 和 VEGF 受体 Flk-1/KDR 之间结构相互作用的影响。对 Flk-1/KDR、caveolin-1 和 eNOS 亚细胞分布的共聚焦免疫定位分析表明，VEGF 刺激所有三种蛋白易位到细胞核中。细胞分级分离和免疫印迹研究证实了这一结果，显示在 VEGF 治疗 30 和 60 分钟后，小凹室内所有三种蛋白质的水平逐渐下降。核分数的模式则相反。对照培养物中的蛋白质水平最低，但在处理 30 和 60 分钟后逐渐增加。小凹内 eNOS 和 Flk-1/KDR 的核易位可能代表了一种将 NO 产生靶向核区室的机制，在核区室中它可以影响转录因子的激活。 (C) 1999 年学术出版社。
VEGF increases endothelial cell permeability and growth by a process requiring NOS activity. Because eNOS activity is regulated by its interaction with the caveolar structural protein caveolin-1, we analyzed VEGF effects on structural interactions between eNOS, caveolin-1 and the VEGF receptor Flk-1/KDR. Confocal immunolocalization analysis of the subcellular distribution of Flk-1/KDR, caveolin-1 and eNOS showed that VEGF stimulated the translocation of all three proteins into the nucleus. This result was confirmed by cell fractionation and immunoblotting studies showing that levels of all three proteins within the caveolar compartment declined progressively after 30 and 60 min of VEGF treatment. The pattern was reversed for nuclear fractions. Protein levels were lowest in the control cultures, but increased progressively after 30 and 60 min of treatment. Nuclear translocation of eNOS and Flk-1/KDR within caveolae may represent a mechanism for targeting NO production to the nuclear compartment where it could influence transcription factor activation. (C) 1999 Academic Press.