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Enhancement of Endothelial Cell Migration and in Vitro Tube Formation by Tap20, a Novel β5 Integrin–Modulating, Pkcθ-Dependent Protein

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      Abstract

      Migration, proliferation, and tube formation of endothelial cells are regulated by a protein kinase C isoenzyme PKCθ. A full-length cDNA encoding a novel 20-kD protein, whose expression was PKCθ-dependent, was identified in endothelial cells, cloned, characterized, and designated as theta-associated protein (TAP) 20. Overexpression of TAP20 decreased cell adhesion and enhanced migration on vitronectin and tube formation in three-dimensional culture. An antiintegrin αvβ5 antibody prevented these TAP20 effects. Overexpression of TAP20 also decreased focal adhesion formation in αvβ3-deficient cells. The interaction between TAP20 and β5 integrin cytoplasmic domain was demonstrated by protein coprecipitation and immunoblotting. Thus, the discovery of TAP20, which interacts with integrin β5 and modulates cell adhesion, migration, and tube formation, further defines a possible pathway to angiogenesis dependent on PKCθ.

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      Most cited references 39

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      Cell migration: a physically integrated molecular process.

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        Integrins: versatility, modulation, and signaling in cell adhesion.

         Thomas Hynes (1992)
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          Cell adhesion: the molecular basis of tissue architecture and morphogenesis.

           B Gumbiner (1996)
          A variety of cell adhesion mechanisms underlie the way that cells are organized in tissues. Stable cell interactions are needed to maintain the structural integrity of tissues, and dynamic changes in cell adhesion participate in the morphogenesis of developing tissues. Stable interactions actually require active adhesion mechanisms that are very similar to those involved in tissue dynamics. Adhesion mechanisms are highly regulated during tissue morphogenesis and are intimately related to the processes of cell motility and cell migration. In particular, the cadherins and the integrins have been implicated in the control of cell movement. Cadherin mediated cell compaction and cellular rearrangements may be analogous to integrin-mediated cell spreading and motility on the ECM. Regulation of cell adhesion can occur at several levels, including affinity modulation, clustering, and coordinated interactions with the actin cytoskeleton. Structural studies have begun to provide a picture of how the binding properties of adhesion receptors themselves might be regulated. However, regulation of tissue morphogenesis requires complex interactions between the adhesion receptors, the cytoskeleton, and networks of signaling pathways. Signals generated locally by the adhesion receptors themselves are involved in the regulation of cell adhesion. These regulatory pathways are also influenced by extrinsic signals arising from the classic growth factor receptors. Furthermore, signals generated locally be adhesion junctions can interact with classic signal transduction pathways to help control cell growth and differentiation. This coupling between physical adhesion and developmental signaling provides a mechanism to tightly integrate physical aspects of tissue morphogenesis with cell growth and differentiation, a coordination that is essential to achieve the intricate patterns of cells in tissues.
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            Author and article information

            Affiliations
            [a]Cardiovascular Division, Department of Medicine, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461
            Contributors
            Journal
            J Cell Biol
            The Journal of Cell Biology
            The Rockefeller University Press
            0021-9525
            1540-8140
            29 November 1999
            : 147
            : 5
            : 1073-1084
            2169340
            9904023
            10579726
            © 1999 The Rockefeller University Press
            Categories
            Original Article

            Cell biology

            migration, endothelial cells, pkcθ, integrin, tap20

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