Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis
Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis
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DOI：
10.1126/science.277.5322.55
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发表时间：
1997-07-04
期刊：
影响因子：
56.9
通讯作者：
Yancopoulos, GD
中科院分区：
文献类型：
--
作者：
Maisonpierre, PC;Suri, C;Yancopoulos, GD
血管生成被认为取决于正调节和负调节的精确平衡。血管生成素-1（Ang 1）是一种血管生成因子，通过内皮细胞特异性Tie 2受体酪氨酸激酶发出信号。与血管内皮生长因子一样，Ang 1对小鼠的正常血管发育至关重要。通过同源性筛选鉴定了Ang 1的相对物，称为血管生成素-2（Ang 2），并显示其为Ang 1和Tie 2的天然拮抗剂。Ang 2的转基因过表达破坏了小鼠胚胎中的血管形成。在成年小鼠和人类中，Ang 2仅在血管重塑部位表达。脊椎动物受体酪氨酸激酶的天然拮抗剂是非典型的，因此，Tie 2的负调节作用的发现强调了这种血管生成受体系统的精细调节的需要。
Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. Like Vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. in adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.