[PDF][PDF] Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands

TCM Seegar, B Eller, D Tzvetkova-Robev, MV Kolev… - Molecular cell, 2010 - cell.com
TCM Seegar, B Eller, D Tzvetkova-Robev, MV Kolev, SC Henderson, DB Nikolov, WA Barton
Molecular cell, 2010cell.com
The Tie family of endothelial-specific receptor tyrosine kinases is essential for cell
proliferation, migration, and survival during angiogenesis. Despite considerable similarity,
experiments with Tie1-or Tie2-deficient mice highlight distinct functions for these receptors in
vivo. The Tie2 receptor is further unique with respect to its structurally homologous ligands.
Angiopoietin-2 and-3 can function as agonists or antagonists; angiopoietin-1 and-4 are
constitutive agonists. To address the role of Tie1 in angiopoietin-mediated Tie2 signaling …
Summary
The Tie family of endothelial-specific receptor tyrosine kinases is essential for cell proliferation, migration, and survival during angiogenesis. Despite considerable similarity, experiments with Tie1- or Tie2-deficient mice highlight distinct functions for these receptors in vivo. The Tie2 receptor is further unique with respect to its structurally homologous ligands. Angiopoietin-2 and -3 can function as agonists or antagonists; angiopoietin-1 and -4 are constitutive agonists. To address the role of Tie1 in angiopoietin-mediated Tie2 signaling and determine the basis for the behavior of the individual angiopoietins, we used an in vivo FRET-based proximity assay to monitor Tie1 and -2 localization and association. We provide evidence for Tie1-Tie2 complex formation on the cell surface and identify molecular surface areas essential for receptor-receptor recognition. We further demonstrate that the Tie1-Tie2 interactions are dynamic, inhibitory, and differentially modulated by angiopoietin-1 and -2. Based on the available data, we propose a unified model for angiopoietin-induced Tie2 signaling.
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