Role of Raf in vascular protection from distinct apoptotic stimuli
Role of Raf in vascular protection from distinct apoptotic stimuli
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DOI：
10.1126/science.1082015
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发表时间：
2003-07-04
期刊：
影响因子：
56.9
通讯作者：
Cheresh, DA
中科院分区：
文献类型：
--
作者：
Alavi, A;Hood, JD;Cheresh, DA
Raf激酶与内皮细胞存活有关。在这里，我们发现碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）不同程度地激活Raf，从而保护人类内皮细胞和鸡胚胎血管的不同凋亡途径。bFGF通过p21活化蛋白激酶-1 （PAK-1）磷酸化丝氨酸338和339激活Raf-1，导致Raf-1线粒体易位和内皮细胞凋亡内在途径的保护，独立于丝裂原活化蛋白激酶-1 （MEK1）。相反，VEGF通过Src激酶激活Raf-1，导致酪氨酸340和341磷酸化，并对外部介导的细胞凋亡产生mek1依赖性保护。这些发现暗示Raf-1是血管生成过程中内皮细胞存活的关键调节因子。
Raf kinases have been linked to endothelial cell survival. Here, we show that basic fibroblast growth factor ( bFGF) and vascular endothelial growth factor ( VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature. bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation of serines 338 and 339, resulting in Raf-1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis, independent of the mitogen-activated protein kinase kinase-1 (MEK1). In contrast, VEGF activated Raf-1 via Src kinase, leading to phosphorylation of tyrosines 340 and 341 and MEK1-dependent protection from extrinsic-mediated apoptosis. These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis.