Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands Journal Article
| Authors: | Seegar, T. C. M.; Eller, B.; Tzvetkova Robev, D.; Kolev, M. V.; Henderson, S. C.; Nikolov, D. B.; Barton, W. A. |
| Article Title: | Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands |
| 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. © 2010 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; mutation; nonhuman; protein conformation; protein localization; mouse; mus; signaling; protein protein interaction; cell line; rna interference; transfection; structure-activity relationship; time factors; endothelial cells; protein multimerization; recombinant fusion proteins; cell membrane; fluorescence resonance energy transfer; ligands; models, molecular; protein structure, tertiary; sequence homology; angiopoietin receptor; receptor, tie-2; angiopoietin 2; cell surface; angiopoietin 1; tie 1 receptor; angiopoietin-1; angiopoietin-2; receptor cross-talk; receptor, tie-1 |
| Journal Title: | Molecular Cell |
| Volume: | 37 |
| Issue: | 5 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2010-03-12 |
| Start Page: | 643 |
| End Page: | 655 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2010.02.007 |
| PUBMED: | 20227369 |
| PROVIDER: | scopus |
| PMCID: | PMC2841065 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 20 April 2011" - "CODEN: MOCEF" - "Source: Scopus" |
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