Inhibition of cultured cell growth by vascular endothelial cadherin (Cadherin-5 VE-cadherin)
Inhibition of cultured cell growth by vascular endothelial cadherin (Cadherin-5 VE-cadherin)
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DOI：
10.1172/jci118870
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发表时间：
1996-08-15
影响因子：
15.9
通讯作者：
Dejana, E
中科院分区：
文献类型：
--
作者：
Caveda, L;MartinPadura, L;Dejana, E
内皮细胞增殖因细胞间接触的建立而受到抑制，因此连接处的粘附分子可以在传递负生长信号中发挥作用，跨膜蛋白VE-钙粘蛋白（血管内皮钙粘蛋白/钙粘蛋白-5）在内皮细胞的细胞间裂隙中选择性表达。细胞内结构域与称为连环蛋白的细胞质蛋白相互作用，后者传递粘附信号并有助于将蛋白锚定到肌动蛋白细胞骨架上。在中国仓鼠卵巢 (CHO) 和 L929 细胞中转染 VE-钙粘蛋白会抑制细胞生长。负责连接连环蛋白的 VE-钙粘蛋白胞质区域的截断不会影响细胞生长。 VE-钙粘蛋白粘附特性，但消除了其对细胞生长的影响，在重组VE-钙粘蛋白氨基末端片段上接种人脐静脉内皮细胞或VE-钙粘蛋白转染子抑制了它们的增殖，这些数据表明，连接处的VE-钙粘蛋白同型接合参与了细胞生长的密度依赖性抑制，这种作用需要细胞外粘附剂 结构域和分子的胞内连环蛋白结合区。
Endothelial cell proliferation is inhibited by the establishment of cell to cell contacts, Adhesive molecules at junctions could therefore play a role in transferring negative growth signals, The transmembrane protein VE-cadherin (vascular endothelial cadherin/cadherin-5) is selectively expressed at intercellular clefts in the endothelium. The intracellular domain interacts with cytoplasmic proteins called catenins that transmit the adhesion signal and contribute to the anchorage of the protein to the actin cytoskeleton, Transfection of VE-cadherin in both Chinese hamster ovary (CHO) and L929 cells confers inhibition of cell growth, Truncation of VE-cadherin cytoplasmic region, responsible for linking catenins, does not affect VE-cadherin adhesive properties but abolishes its effect on cell growth, Seeding human umbilical vein endothelial cells or VE-cadherin transfectants on a recombinant VE-cadherin amino-terminal fragment inhibited their proliferation, These data show that VE-cadherin homotypic engagement at junctions participates in density dependent inhibition Of cell growth, This effect requires both the extracellular adhesive domain and the intracellular catenin binding region of the molecule.