Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability
Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability
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DOI：
10.1016/s1097-2765(00)80221-x
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发表时间：
1999-12-01
期刊：
影响因子：
16
通讯作者：
Cheresh, DA
中科院分区：
文献类型：
--
作者：
Eliceiri, BP;Paul, R;Cheresh, DA
研究发现，在鸡胚和小鼠中，在血管内皮生长因子 (VEGF)（而非碱性成纤维细胞生长因子 (bFGF)）介导的血管生成过程中，Src 激酶活性可以保护内皮细胞免于凋亡。事实上，逆转录病毒将激酶缺失的 Src 靶向肿瘤相关血管，抑制了血管生成和产生 VEGF 的肿瘤的生长。尽管缺乏单个Src家族激酶（SFK）的小鼠显示出正常的血管生成，但缺乏pp60（c-src）或pp62（c-yes）的小鼠未显示出VEGF诱导的血管通透性（VP），而fyn（-/-）小鼠则显示出正常的VP。相比之下，Src 缺陷小鼠中炎症介导的 VP 表现正常。因此，VEGF介导的血管生成一般需要SFK活性，而bFGF介导的血管生成则不需要，而VEGF的VP活性具体取决于SFK、Src或Yes。
Src kinase activity was found to protect endothelial cells from apoptosis during vascular endothelial growth factor (VEGF)-, but not basic fibroblast growth factor (bFGF)-, mediated angiogenesis in chick embryos and mice. In fact, retroviral targeting of kinase-deleted Src to tumor-associated blood vessels suppressed angiogenesis and the growth of a VEGF-producing tumor. Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60(c-src) or pp62(c-yes) showed no VEGF-induced vascular permeability (VP), yet fyn(-/-) mice displayed normal VP. In contrast, inflammation-mediated VP appeared normal in Src-deficient mice. Therefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFKs, Src, or Yes.