title: Influence of PECAM-1 ligand interactions on PECAM-1-dependent cell motility and filopodia extension.
abstract: Platelet endothelial cell adhesion molecule (PECAM-1) has been implicated in angiogenesis through processes that involve stimulation of endothelial cell motility. Previous studies suggest that PECAM-1 tyrosine phosphorylation mediates the recruitment and then activation of the tyrosine phosphatase SHP-2, which in turn promotes the turnover of focal adhesions and the extension of filopodia, processes critical to cell motility. While these studies have implicated PECAM-1-dependent signaling in PECAM-1-mediated cell motility, the involvement of PECAM-1 ligand binding in cell migration is undefined. Therefore to investigate the role of PECAM-1 binding interactions in cell motility, mutants of PECAM-1 were generated in which either homophilic or heparin/glycosaminoglycan (GAG)-mediated heterophilic binding had been disabled and then expressed in an endothelial cell surrogate. We found that the ability of PECAM-1 to stimulate cell migration, promote filopodia formation and trigger Cdc42 activation were lost if PECAM-1-dependent homophilic or heparin/GAG-dependent heterophilic ligand binding was disabled. We further observed that PECAM-1 concentrated at the tips of extended filopodia, an activity that was diminished if homophilic, but not heparin/GAG-mediated heterophilic binding had been disrupted. Similar patterns of activities were seen in mouse endothelial cells treated with antibodies that specifically block PECAM-1-dependent homophilic or heterophilic adhesion. Together these data provide evidence for the differential involvement of PECAM-1-ligand interactions in PECAM-1-dependent motility and the extension of filopodia.
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Valsamma
authors.initials: V
authors.lastname: Abraham
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Andrew
authors.initials: A
authors.lastname: Parambath
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Debria S
authors.initials: DS
authors.lastname: Joe
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania delisser@mail.med.upenn.edu.
authors.forename: Horace M
authors.initials: HM
authors.lastname: DeLisser
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015478:Antigens, Heterophile; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; PECAM‐1; endothelial cells; filopodia; motility