Mechanisms of Integrin–Vascular Endothelial Growth Factor Receptor Cross-Activation in Angiogenesis

• DOI: 10.1161/circresaha.107.155655
• Publication Date: 2007-07-20T01:14:51Z
• Authors: Ganapati H. Mahab...; Weiyi Feng; Kumar Reddy; Edward F. Plow; Tatiana V. Byzova
• Keywords: Cytoplasm; Indoles; Integrin beta3; Endothelial Cells; Neovascularization, Physiologic; Receptor Cross-Talk; Integrin alphaVbeta3; Kinetics; Mice; Cell Movement; Multiprotein Complexes; Cell Adhesion; Animals; Humans; Collagen; Laminin; Phosphorylation; Protein Kinase Inhibitors; Cells, Cultured; Signal Transduction

The functional responses of endothelial cells are dependent on signaling from peptide growth factors and the cellular adhesion receptors, integrins. These include cell adhesion, migration, proliferation, which, in turn, essential for more complex processes such as formation tube network during angiogenesis. This study identifies molecular requirements cross-activation between beta3 integrin tyrosine kinase receptor 2 vascular factor (VEGF) (VEGFR-2) endothelium. relationship VEGFR-2 appears to be synergistic, because activation induces phosphorylation, is crucial VEGF-induced phosphorylation VEGFR-2. We demonstrate here that adhesion- factor-induced directly mediated by c-Src. VEGF-stimulated recruitment c-Src subsequent critical interaction integrin. Moreover, mediates activation, ligand binding, integrin-dependent directional migration cells, initiation angiogenic programming cells. Thus, present determines mechanisms consequences synergism surface systems, integrins, opens new avenues development pro- antiangiogenic strategies.