Angiopoietin-2 stimulation of endothelial cells induces αvβ3 integrin internalization and degradation
The angiopoietins (Ang-1 and Ang-2) have been identified as agonistic and antagonistic ligands of the endothelial receptor tyrosine kinase Tie2, respectively. Both ligands have been demonstrated to induce translocation of Tie2 to cell-cell junctions. However, only Ang-1 induces Tie2-dependent Akt ac...
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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2 June 2010
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| In: |
The journal of biological chemistry
Year: 2010, Jahrgang: 285, Heft: 31, Pages: 23842-23849 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M109.097543 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M109.097543 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0021925820618506 
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| Verfasserangaben: | Markus Thomas, Moritz Felcht, Karoline Kruse, Stella Kretschmer, Carleen Deppermann, Andreas Biesdorf, Karl Rohr, Andrew V. Benest, Ulrike Fiedler, and Hellmut G. Augustin |
| Zusammenfassung: | The angiopoietins (Ang-1 and Ang-2) have been identified as agonistic and antagonistic ligands of the endothelial receptor tyrosine kinase Tie2, respectively. Both ligands have been demonstrated to induce translocation of Tie2 to cell-cell junctions. However, only Ang-1 induces Tie2-dependent Akt activation and subsequent survival signaling and endothelial quiescence. Ang-2 interferes negatively with Ang-1/Tie2 signaling, thereby antagonizing the Ang-1/Tie2 axis. Here, we show that both Ang-1 and Ang-2 recruit β3 integrins to Tie2. This co-localization is most prominent in cell-cell junctions. However, only Ang-2 stimulation resulted in complex formation among Tie2, αvβ3 integrin, and focal adhesion kinase as evidenced by co-immunoprecipitation experiments. Focal adhesion kinase was phosphorylated in the FAT domain at Ser910 upon Ang-2 stimulation and the adaptor proteins p130Cas and talin dissociated from αvβ3 integrin. The αvβ3 integrin was internalized, ubiquitinylated, and gated toward lysosomes. Taken together, the experiments define Tie2/αvβ3 integrin association-induced integrin internalization and degradation as mechanistic consequences of endothelial Ang-2 stimulation. |
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| Beschreibung: | Gesehen am 15.11.2023 |
| Beschreibung: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M109.097543 |