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Mol Cell. 2010 Mar 12;37(5):643-55. doi: 10.1016/j.molcel.2010.02.007.

Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands.

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  • 1Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298, USA.

Abstract

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.

(c) 2010 Elsevier Inc. All rights reserved.

PMID:
20227369
[PubMed - indexed for MEDLINE]
PMCID:
PMC2841065
Free PMC Article
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