| Title |
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Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor
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| Creator |
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Theodoropoulou, Christina
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Megalooikonomou, Vasileios
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Papadimitriou, Evangelia
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| Accessrights |
open access |
| Rights |
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| Subject |
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Other
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Chondroitin sulphate
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Other
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Endothelial cells
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Other
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Migration
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Other
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Pleiotrophin
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Other
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Tyrosine phosphatases
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Other
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Vascular endothelial growth factor
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NDC
460
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| Description |
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Abstract
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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.
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Biomed Central Ltd
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| Resource Type |
journal article |
| Version Type |
VoR |
| Identifier |
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http://hdl.handle.net/2115/62916
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| Relation |
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isIdenticalTo
DOI
https://doi.org/10.1186/s12943-015-0287-3
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PMID
25644401
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| Journal |
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Molecular Cancer
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Volume Number14
Page Start19
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| File |
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| Oaidate |
2023-07-26 |
