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血管新生选择性地需要PI3K的p110alpha异型来控制内皮细胞迁移
Mariona Graupera1, Julie Guillermet-Guibert, Lazaros C Foukas
1Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.
Nature
|May 2, 2008
概括
酸-3-酶 (PI3Ks) 对于血管发育至关重要. 只有p110alpha活性对于血管生成期间的内皮细胞迁移和血管重塑至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 发育生物学 发展生物学
背景情况:
- 酸3-酶 (PI3Ks) 是各种细胞表面受体下游的关键信号酶.
- 由p110催化和p85调节子单元组成的IA类PI3K异型,涉及血管生成.
- 在体内血管生成过程中,PI3Ks在内皮细胞中的特定作用和同型选择性在很大程度上是未知的.
研究的目的:
- 在血管生成过程中研究PI3K信号在内皮细胞中的体内功能和异形选择性.
- 确定关键的PI3K异型及其下游调节血管发育的作用因子.
主要方法:
- 利用无处不在和内皮细胞特异性基因失活模型来研究p110alpha功能.
- 评估了胚胎死亡率,血管发芽和血管重塑缺陷.
- 研究了通过小GTPase RhoA.通过内皮细胞迁移的调节.
主要成果:
- 内皮细胞特异性的p110alpha无活化导致胚胎致死性,原因是血管发芽和血管重塑的严重缺陷.
- p110alpha活性对于内皮细胞迁移至关重要,通过RhoA.作用.
- p110alpha在内皮细胞中高度表达,并优先由氨酸激酶配体如VEGF-A诱导.
- p110beta信号下游的GPCR配体 (例如,SDF-1alpha),而p110delta对内皮细胞PI3K活动的贡献很小.
结论:
- p110alpha活性对于血管发育和血管生成至关重要,具有内皮细胞自主功能.
- 在体内表现出PI3K信号在内皮细胞中的异形选择性,p110alpha起着关键作用.
- 在血管生成过程中通过RhoA识别了p110alpha作为内皮细胞迁移的关键调节者.
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