Cloning and characterization of developmental endothelial locus-1:: An embryonic endothelial cell protein that binds the αvβ3 integrin receptor

被引:200
作者
Hidai, C
Zupancic, T
Penta, K
Mikhail, A
Kawana, M
Quertermous, EE
Aoka, Y
Fukagawa, M
Matsui, Y
Platika, D
Auerbach, R
Hogan, BLM
Snodgrass, R
Quertermous, T
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, Howard Hughes Med Inst, Nashville, TN 37232 USA
[5] Tokyo Womens Med Coll, Tokyo 162, Japan
[6] Progenitor Inc, Menlo Park, CA 94025 USA
[7] Univ Tokyo, Dept Internal Med 3, Tokyo 113, Japan
[8] Tohoku Univ, Inst Dev Aging & Canc, Dept Cell Biol, Sendai, Miyagi 980, Japan
[9] Univ Wisconsin, Dept Zool, Madison, WI 53202 USA
关键词
endothelial; integrin; cloning; angiogenesis; embryogenesis; vasculature;
D O I
10.1101/gad.12.1.21
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 alpha v beta 3 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 alpha v beta 3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.
引用
收藏
页码:21 / 33
页数:13
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