|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
Peer-reviewed Journal Articles, etc >
Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor |
| Authors: | Koutsioumpa, Marina Browse this author | | Poimenidi, Evangelia Browse this author | | Pantazaka, Evangelia Browse this author | | Theodoropoulou, Christina Browse this author | | Skoura, Angeliki Browse this author | | Megalooikonomou, Vasileios Browse this author | | Kieffer, Nelly Browse this author | | Courty, Jose Browse this author | | Mizumoto, Shuji Browse this author | | Sugahara, Kazuyuki Browse this author →KAKEN DB | | Papadimitriou, Evangelia Browse this author |
| Keywords: | Chondroitin sulphate | | Endothelial cells | | Migration | | Pleiotrophin | | Tyrosine phosphatases | | Vascular endothelial growth factor |
| Issue Date: | 3-Feb-2015 |
| Publisher: | Biomed Central Ltd |
| Journal Title: | Molecular Cancer |
| Volume: | 14 |
| Start Page: | 19 |
| Publisher DOI: | 10.1186/s12943-015-0287-3 |
| PMID: | 25644401 |
| Abstract: | Background: Receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) is a chondroitin sulphate (CS) transmembrane protein tyrosine phosphatase and is a receptor for pleiotrophin (PTN). RPTPβ/ζ interacts with ανβ3 on the cell surface and upon binding of PTN leads to c-Src dephosphorylation at Tyr530, β3 Tyr773 phosphorylation, cell surface nucleolin (NCL) localization and stimulation of cell migration. c-Src-mediated β3 Tyr773 phosphorylation is also observed after vascular endothelial growth factor 165 (VEGF165) stimulation of endothelial cells and is essential for VEGF receptor type 2 (VEGFR2) - ανβ3 integrin association and subsequent signaling. In the present work, we studied whether RPTPβ/ζ mediates angiogenic actions of VEGF. Methods: Human umbilical vein endothelial, human glioma U87MG and stably transfected Chinese hamster ovary cells expressing different β3 subunits were used. Protein-protein interactions were studied by a combination of immunoprecipitation/Western blot, immunofluorescence and proximity ligation assays, properly quantified as needed. RPTPβ/ζ expression was down-regulated using small interference RNA technology. Migration assays were performed in 24-well microchemotaxis chambers, using uncoated polycarbonate membranes with 8 μm pores. Results: RPTPβ/ζ mediates VEGF165-induced c-Src-dependent β3 Tyr773 phosphorylation, which is required for VEGFR2-ανβ3 interaction and the downstream activation of phosphatidylinositol 3-kinase (PI3K) and cell surface NCL localization. RPTPβ/ζ directly interacts with VEGF165, and this interaction is not affected by bevacizumab, while it is interrupted by both CS-E and PTN. Down-regulation of RPTPβ/ζ by siRNA or administration of exogenous CS-E abolishes VEGF165-induced endothelial cell migration, while PTN inhibits the migratory effect of VEGF165 to the levels of its own effect. Conclusions: These data identify RPTPβ/ζ as a cell membrane binding partner for VEGF that regulates angiogenic functions of endothelial cells and suggest that it warrants further validation as a potential target for development of additive or alternative anti-VEGF therapies. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/62916 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 菅原 一幸
|
