Del1 Induces Integrin Signaling and Angiogenesis by Ligation of αVβ3

• Published in: The Journal of biological chemistry Vol. 274; no. 16; p. 11101
• Main Authors: Kalyani Penta, Judith A. Varner, Lucy Liaw, Chiaki Hidai, Randy Schatzman, Thomas Quertermous
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 16-04-1999
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.16.11101

Del1 is a novel extracellular matrix protein encoding three Notch-like epidermal growth factor repeats, an RGD motif, and
two discoidin domains. Del1 is expressed in an endothelial cell-restricted pattern during early development. In studies reported
here, recombinant baculovirus Del1 protein was shown to promote αvβ3-dependent endothelial cell attachment and migration.
Attachment of endothelial cells to Del1 was associated with clustering of αvβ3, the formation of focal complexes, and recruitment
of talin and vinculin into these complexes. These events were shown to be associated with phosphorylation of proteins in the
focal complexes, including the time-dependent phosphorylation of p125 FAK , MAPK, and Shc. When recombinant Del1 was evaluated in an in ovo chick chorioallantoic membrane assay, it was found to have potent angiogenic activity. This angiogenic activity was inhibited
by a monoclonal antibody directed against αvβ3, and an RAD mutant Del1 protein was inactive. Thus Del1 provides a unique autocrine
angiogenic pathway for the embryonic endothelium, and this function is mediated in part by productive ligation of integrin
αvβ3.