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Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell–cell and cell–matrix contacts

Saharinen, Pipsa, Eklund, Lauri, Miettinen, Juho, Wirkkala, Riikka, Anisimov, Andrey, Winderlich, Mark, Nottebaum, Astrid, Vestweber, Dietmar +4 more·2008·Nature Cell Biology
DOI 10.1038/ncb1715
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Abstract

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.

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Crossref · 10.1038/ncb1715

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  • Both pericytes and astrocytes can release Angiopoietin-1 that binds to endothelial Tie-2 receptors to improve brain vascular integrity.

    “both pericytes and astrocytes can release Angiopoietin-1 that binds to endothelial Tie-2 receptors to improve brain vascular integrity45,46.”

    From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [46]

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Authors
Saharinen, P., Eklund, L., Miettinen, J., Wirkkala, R., Anisimov, A., Winderlich, M., Nottebaum, A., Vestweber, D., Deutsch, U., Koh, G. Y., Olsen, B. R., & Alitalo, K.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2008-04-20
Volume
10
Issue
5
Pages
527-537
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb1715
Cited by
415
References
2
Language
en
Licence
www.springer.com/tdm (tdm)

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