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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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Main Authors: Thomas, Markus (Author) , Felcht, Moritz (Author) , Kruse, Karoline (Author) , Kretschmer, Stella (Author) , Deppermann, Carleen (Author) , Biesdorf, Andreas (Author) , Rohr, Karl (Author) , Benest, Andrew V. (Author) , Fiedler, Ulrike (Author) , Augustin, Hellmut (Author)
Format: Article (Journal)
Language:English
Published: 2 June 2010
In: The journal of biological chemistry
Year: 2010, Volume: 285, Issue: 31, Pages: 23842-23849
ISSN:1083-351X
DOI:10.1074/jbc.M109.097543
Online Access: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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Author Notes:Markus Thomas, Moritz Felcht, Karoline Kruse, Stella Kretschmer, Carleen Deppermann, Andreas Biesdorf, Karl Rohr, Andrew V. Benest, Ulrike Fiedler, and Hellmut G. Augustin
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Summary: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.
Item Description:Gesehen am 15.11.2023
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M109.097543

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