Regulating angiogenesis at the level of PtdIns-4,5-P2
Regulating angiogenesis at the level of PtdIns-4,5-P2
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DOI：
10.1038/sj.emboj.7601100
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发表时间：
2006-05-17
期刊：
影响因子：
11.4
通讯作者：
Kazlauskas, Andrius
中科院分区：
文献类型：
--
作者：
Im, Eunok;Kazlauskas, Andrius
血管生成是导致新血管生长的细胞反应的协调序列。血管生成程序由细胞外因子调节，其输入至少部分地在由磷酸肌醇3激酶（PI 3 K）和磷脂酶C γ（PLC γ）驱动的信号转导途径水平上整合。使用体外血管生成模型，我们发现PI 3 K是管形成所必需的，而PLC γ促进消退。PLC γ拮抗管形成的潜在机制似乎是通过与PI 3 K竞争它们的共同底物磷脂酰肌醇-4，5-二磷酸。这些研究是第一个确定参与血管退化的信号酶，并揭示了血管生成程序可以通过膜脂质的可用性来协调。
Angiogenesis is a coordinated sequence of cellular responses that result in the outgrowth of new blood vessels. The angiogenic program is regulated by extracellular factors, whose input is integrated at least in part at the level of signal transduction pathways driven by phosphoinositide 3 kinase (PI3K) and phospholipase C gamma (PLC gamma). Using an in vitro angiogenesis model, we discovered that PI3K was essential for tube formation, whereas PLC gamma promoted regression. The underlying mechanism by which PLC gamma antagonized tube formation appeared to be by competing with PI3K for their common substrate, phosphatidylinositol-4,5-bisphosphate. These studies are the first to identify signaling enzymes involved with vessel regression, and reveal that the angiogenic program can be coordinated by the availability of a membrane lipid.