DISTINCT ROLES OF THE RECEPTOR TYROSINE KINASES TIE-1 AND TIE-2 IN BLOOD-VESSEL FORMATION

DISTINCT ROLES OF THE RECEPTOR TYROSINE KINASES TIE-1 AND TIE-2 IN BLOOD-VESSEL FORMATION
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DOI:
10.1038/376070a0
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发表时间:
1995-07-06
期刊:
影响因子:
64.8
通讯作者:
QIN, Y
QIN, Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SATO, TN;TOZAWA, Y;QIN, Y

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TIE-1和Tie-2定义了一类新的受体酪氨酸激酶,它们在发育中的血管内皮细胞中特异性表达。为了研究Tie-1和Tie-2在体内血管内皮细胞生长和分化过程中的功能,通过同源重组将小鼠的基因定向突变。Tie-1缺陷的胚胎未能建立血管内皮细胞的结构完整性,导致水肿和随后的局部出血。然而,对Tie-2缺陷的胚胎的分析表明,它在血管生成中很重要,特别是对于内皮细胞中的血管网络形成。这一结果与以前关于Tie-2在血管发生和/或内皮细胞存活中的功能的报道形成对比。我们的体内分析表明,结构相关的受体酪氨酸激酶Tie-1和Tie-2在血管的形成中具有重要但不同的作用。
TIE-1 and Tie-2 define a new class of receptor tyrosine kinases that are specifically expressed in developing vascular endothelial cells. To study the functions of Tie-1 and Tie-2 during vascular endothelial cell growth and differentiation in vivo, targeted mutations of the genes in mice were introduced by homologous recombination. Embryos deficient in Tie-1 failed to establish structural integrity of vascular endothelial cells, resulting in oedema and subsequently localized haemorrhage. However, analyses of embryos deficient in Tie-2 showed that it is important in angiogenesis, particularly for vascular network formation in endothelial cells. This result contrasts with previous reports on Tie-2 function in vasculogenesis and/or endothelial cen survival. Our in vivo analyses indicate that the structurally related receptor tyrosine kinases Tie-1 and Tie-2 have important hut distinct roles in the formation of blood vessels.