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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2770-2779. Prepublished online as a Blood First Edition Paper on July 18, 2008; DOI 10.1182/blood-2008-03-147181. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2008-03-147181v1 112/7/2770    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Alcaide, P. Articles by Luscinskas, F. W. Search for Related Content PubMed PubMed Citation Articles by Alcaide, P. Articles by Luscinskas, F. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY p120-Catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation Pilar Alcaide1, Gail Newton1, Scott Auerbach1, Seema Sehrawat1, Tanya N. Mayadas1, David E. Golan2, Patrick Yacono2, Peter Vincent3, Andrew Kowalczyk4, and Francis W. Luscinskas1 1 Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; 2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA; 3 The Center for Cardiovascular Sciences, Albany Medical College, NY; and 4 Department of Dermatology, The Emory Skin Diseases Research Center, Atlanta, GA Vascular endothelial–cadherin (VE-cad) is localized to adherens junctions at endothelial cell borders and forms a complex with -, β-, -, and p120-catenins (p120). We previously showed that the VE-cad complex disassociates to form short-lived "gaps" during leukocyte transendothelial migration (TEM); however, whether these gaps are required for leukocyte TEM is not clear. Recently p120 has been shown to control VE-cad surface expression through endocytosis. We hypothesized that p120 regulates VE-cad surface expression, which would in turn have functional consequences for leukocyte transmigration. Here we show that endothelial cells transduced with an adenovirus expressing p120GFP fusion protein significantly increase VE-cad expression. Moreover, endothelial junctions with high p120GFP expression largely prevent VE-cad gap formation and neutrophil leukocyte TEM; if TEM occurs, the length of time required is prolonged. We find no evidence that VE-cad endocytosis plays a role in VE-cad gap formation and instead show that this process is regulated by changes in VE-cad phosphorylation. In fact, a nonphosphorylatable VE-cad mutant prevented TEM. In summary, our studies provide compelling evidence that VE-cad gap formation is required for leukocyte transmigration and identify p120 as a critical intracellular mediator of this process through its regulation of VE-cad expression at junctions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. A. Muller Mechanisms of Transendothelial Migration of Leukocytes Circ. Res., July 31, 2009; 105(3): 223 - 230. [Abstract] [Full Text] [PDF]

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