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First published online 17 January 2006
doi: 10.1242/jcs.02771
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Research Article |
vß3 specific
1 Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
2 Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA
3 Delaware Biotechnology Institute, University of Delaware, Newark, DE 19716, USA
* Author for correspondence (e-mail: unaik{at}udel.edu)
Accepted 31 October 2005
Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin superfamily, and is mainly expressed in the tight junctions of both epithelial and endothelial cells. We have recently shown that JAM-A is involved in basic fibroblast growth factor (bFGF)-induced angiogenesis. Here, we show that, when ectopically expressed in human umbilical vein endothelial cells (HUVECs), JAM-A induced enhanced cell migration on vitronectin, but had no effect on fibronectin. Use of antibodies that block integrin function indicated that the migration on vitronectin is specific to integrin 
vß3 and not to integrin vß5. JAM-A-induced migration was inhibited by anti-JAM-A antibody. Additionally, overexpression of a JAM-A cytoplasmic domain deletion mutant failed to induce HUVEC migration. Addition of phosphoinositide 3-kinase and protein kinase C inhibitors blocked JAM-A-induced migration, suggesting that these kinases act downstream of JAM-A. Immunoprecipitation analysis showed that JAM-A interacts with integrin vß3, and this association was increased by engagement of the ligand-binding site of the integrin by Arg-Gly-Asp-Ser (RGDS) peptide. Furthermore, activation of both focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) on vitronectin was enhanced by JAM-A overexpression but not by its cytoplasmic domain deletion mutant. Taken together, these results suggest that signaling through JAM-A is necessary for vß3-dependent HUVEC migration and implicate JAM-A in the regulation of vascular function.
Key words: Junctional adhesion molecule, Endothelial cell migration, F11R, Integrin vß3, Vitronectin, MAPK
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