Hidai C, Zupancic T, Penta K, Mikhail A, Kawana M, Quertermous E E, Aoka Y, Fukagawa M, Matsui Y, Platika D, Auerbach R, Hogan B L, Snodgrass R, Quertermous T
Tokyo Women's Medical College, Tokyo 162, Japan.
Genes Dev. 1998 Jan 1;12(1):21-33. doi: 10.1101/gad.12.1.21.
We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including an EGF-like repeat that contains an RGD motif, and two discoidin I-like domains. Del1 is shown to be a matrix protein and to promote adhesion of endothelial cells through interaction with the alphavbeta3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alphavbeta3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.
我们利用转基因小鼠品系中的增强子捕获事件，鉴定出一个独特的、受发育调控的内皮细胞位点（Del1）。该位点编码的蛋白质包含三个与Notch及相关蛋白中的表皮生长因子（EGF）样重复序列同源的序列，其中一个EGF样重复序列含有RGD基序，还有两个盘状结构域I样结构域。研究表明，Del1是一种基质蛋白，可通过与αvβ3整合素受体相互作用促进内皮细胞黏附。表达重组Del1蛋白或在含有Del1蛋白的细胞外基质上生长的胚胎内皮样卵黄囊细胞，形成血管样结构的能力受到抑制。在鸡绒毛尿囊膜中表达Del1蛋白会导致血管完整性丧失，并促进血管重塑。因此，Del1是αvβ3整合素受体的一种新配体，可能在胚胎发育过程中调节血管形态发生或重塑。
