Affiliation:
1. From the Department of Biological Sciences, University of Delaware, Newark; Albany College of Pharmacy, NY; and Epithelial Pathobiology Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, GA.
Abstract
AbstractGrowth factor–induced neovascularization has received a great deal of attention because it is fundamental to the growth and metastasis of solid tumors. This multistep process requires extensive signaling through growth factor receptors and integrins. Among the integrins involved in this process, integrin αvβ3 is specific to basic fibroblast growth factor (bFGF)–induced angiogenesis. Here we show that junctional adhesion molecule 1/A (JAM-1/A) and αvβ3 form a complex in the absence of bFGF. JAM-1, which is normally localized at the cell-cell junctions of quiescent endothelial cells, redistributes to the cell surface on bFGF treatment. Blockage of the extracellular domain of JAM-1 inhibits bFGF-induced endothelial cell morphology, proliferation, and angiogenesis. Additionally, mutation in the JAM-1 cytoplasmic domain blocks bFGF-induced mitogen-activated protein (MAP) kinase activation and ablates its ability to induce endothelial cell tube formation, suggesting that signaling through JAM-1 is key to bFGF-induced signaling. Immunoprecipitation analysis suggests that bFGF signaling dissociates the JAM-1/ αvβ3 complex, allowing for signaling through JAM-1 and αvβ3. In addition, blockage of either JAM-1 or αvβ3 inhibits bFGF-induced MAP kinase activation. Thus, our results suggest that signaling through JAM-1 and αvβ3 is necessary for bFGF-induced angiogenesis.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
128 articles.
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