Saharinen, Pipsa; Eklund, Lauri; Miettinen, Juho; Wirkkala, Riikka; Anisimov, Andrey; Winderlich, Mark; Nottebaum, Astrid; Vestweber, Dietmar; Deutsch, Urban; Koh, Gou Young; Olsen, Bjorn R; Alitalo, Kari (2008). Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nature cell biology, 10(5), pp. 527-37. London: Nature Publishing Group 10.1038/ncb1715
Full text not available from this repository. (Request a copy)The receptor tyrosine kinase Tie2, and its activating ligand Angiopoietin-1 (Ang1), are required for vascular remodelling and vessel integrity, whereas Ang2 may counteract these functions. However, it is not known how Tie2 transduces these different signals. Here, we show that Ang1 induces unique Tie2 complexes in mobile and confluent endothelial cells. Matrix-bound Ang1 induced cell adhesion, motility and Tie2 activation in cell-matrix contacts that became translocated to the trailing edge in migrating endothelial cells. In contrast, in contacting cells Ang1 induced Tie2 translocation to cell-cell contacts and the formation of homotypic Tie2-Tie2 trans-associated complexes that included the vascular endothelial phosphotyrosine phosphatase, leading to inhibition of paracellular permeability. Distinct signalling proteins were preferentially activated by Tie2 in the cell-matrix and cell-cell contacts, where Ang2 inhibited Ang1-induced Tie2 activation. This novel type of cellular microenvironment-dependent receptor tyrosine kinase activation may explain some of the effects of angiopoietins in angiogenesis and vessel stabilization.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Deutsch, Urban |
ISSN: |
1465-7392 |
ISBN: |
18425119 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:05 |
Last Modified: |
05 Dec 2022 14:20 |
Publisher DOI: |
10.1038/ncb1715 |
PubMed ID: |
18425119 |
Web of Science ID: |
000255502400009 |
URI: |
https://boris.unibe.ch/id/eprint/28204 (FactScience: 118534) |
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