Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor.
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.
Hidai
C
C
Tokyo Women's Medical College, Tokyo 162, Japan.
Zupancic
T
T
Penta
K
K
Mikhail
A
A
Kawana
M
M
Quertermous
E E
EE
Aoka
Y
Y
Fukagawa
M
M
Matsui
Y
Y
Platika
D
D
Auerbach
R
R
Hogan
B L
BL
Snodgrass
R
R
Quertermous
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004730:Endothelium, Vascular / Q000196:embryology / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D012313:RNA; D019030:Receptors, Vitronectin / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; C110183:EDIL3 protein, human; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D019030:Receptors, Vitronectin; D012313:RNA