Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor
| Autor: | Evangelia Poimenidi, Vasileios Megalooikonomou, José Courty, Evangelia Papadimitriou, Nelly Kieffer, Angeliki Skoura, Kazuyuki Sugahara, Evangelia Pantazaka, Shuji Mizumoto, Marina Koutsioumpa, Christina Theodoropoulou |
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| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Integrins Endothelial cells Integrin Down-Regulation Protein tyrosine phosphatase CHO Cells Biology Pleiotrophin Cell Line chemistry.chemical_compound Phosphatidylinositol 3-Kinases Cricetulus Cell Movement Tyrosine phosphatases Human Umbilical Vein Endothelial Cells Animals Humans Protein Interaction Maps Phosphorylation RNA Small Interfering Migration Receptor-Like Protein Tyrosine Phosphatases Class 5 Research Glioma Molecular biology Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A Oncology chemistry biology.protein Molecular Medicine Chondroitin sulphate Nucleolin Protein Binding |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0287-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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