Constitutive Association of Tie1 and Tie2 with Endothelial Integrins is Functionally Modulated by Angiopoietin-1 and Fibronectin

• DOI: 10.1371/journal.pone.0163732
• Publication Date: 2016-10-03T13:45:17Z
• Authors: Annamarie C. Dalton; Tomer Shlamkovitch; Niv Papo; William A. Barton
• Keywords: Angiopoietin receptor

Functional cross-talk between Tie2 and Integrin signaling pathways is essential to coordinate endothelial cell adhesion migration in response the extracellular matrix, yet mechanisms behind this phenomenon are unclear. Here, we examine possibility that receptor driven through uncharacterized Tie-integrin interactions on surface. Using a live FRET-based proximity assay, monitor recognition demonstrate both Tie1 readily associate with integrins α5ß1 αVß3 their respective ectodomains. Although not required, Tie2-integrin association significantly enhanced presence of component integrin ligand fibronectin. In vitro binding assays purified components reveal direct, further domain Ang-1, but Ang-2, can independently or αVß3. Finally, cooperative Tie/integrin selectively stimulate ERK/MAPK Ang-1 fibronectin, suggesting molecular mechanism sensitize matrix. We provide mechanistic model highlighting role localization regulating distinct cascades turn, angiogenic switch.