Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin is integrin alpha v beta 3 specific.
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 alpha(v)beta(3) and not to integrin alpha(v)beta(5). 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 alpha(v)beta(3), 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 alpha(v)beta(3)-dependent HUVEC migration and implicate JAM-A in the regulation of vascular function.
Naik
Meghna U
MU
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA. unaik@udel.edu
Naik
Ulhas P
UP
D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology*; D019096:Vitronectin / Q000378:metabolism
D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D007136:Immunoglobulins; D039302:Integrin alphaVbeta3; D011956:Receptors, Cell Surface; D019096:Vitronectin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases