Stable interaction between α5β1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1
Open accessAbstract
During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could cross-talk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that α5β1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and α5β1 interact constitutively; α5β1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively α5β1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and α5β1 receptors that could cross-talk when Tie2/α5β1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that α5β1, but not αvβ3 activation, is essential to Ang-1–dependent angiogenesis in vivo.
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- Authors
- Cascone, I., Napione, L., Maniero, F., Serini, G., & Bussolino, F.
- Affiliations
- University of Turin (IT)
- Corresponding author
- Cascone, Ilaria
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-09-12
- Volume
- 170
- Issue
- 6
- Pages
- 993-1004
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2171441
- OpenAlex
- W2115566079
- Cited by
- 179
- References
- 79
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- FWCI
- 6.38
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- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
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- cc-by-nc-sa
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- PubMed Central (publishedVersion, cc-by-nc-sa)
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- Funders
- Compagnia di San Paolo
- Ministero della Salute
- Istituto Superiore di Sanità
- Associazione Italiana per la Ricerca sul Cancro
- Regione Piemonte
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- alpha5beta1 integrin, Tie2 receptor, angiopoietin-1, angiogenesis, endothelial cells, fibronectin, focal adhesion kinase, p85, endothelial cell motility, endothelial cell survival, vessel stabilization
- MeSH terms
- Animals, Cell Adhesion, Cell Line, Cell Movement, Cell Survival, Chick Embryo, Chromones, Cricetulus, Dose-Response Relationship, Drug, Endothelium, Vascular, Fibrinogen, Fibronectins, Cricetinae, Humans, Kinetics, Morpholines, Precipitin Tests, Umbilical Veins, CHO Cells, Neovascularization, Physiologic, Cell Culture Techniques, Collagen Type I, Integrin alpha5beta1, Angiopoietin-1, Receptor, TIE-2, Chorioallantoic Membrane
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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