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Title
  • Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor
Creator

Koutsioumpa, Marina

Poimenidi, Evangelia

Pantazaka, Evangelia

Theodoropoulou, Christina

Skoura, Angeliki

Megalooikonomou, Vasileios

Kieffer, Nelly

Courty, Jose

Mizumoto, Shuji

Sugahara, Kazuyuki

NRID 1000060154449

Papadimitriou, Evangelia

Rights
    • https://creativecommons.org/licenses/by/4.0/
Subject
  • Other Chondroitin sulphate
  • Other Endothelial cells
  • Other Migration
  • Other Pleiotrophin
  • Other Tyrosine phosphatases
  • Other Vascular endothelial growth factor
  • NDC 460
Description
Other
  • 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.
PublisherBiomed Central Ltd
Date Issued 2015-02-03
Languageeng
NIItypejournal article
VersiontypeVoR
Identifier URI http://hdl.handle.net/2115/62916
Relation
  • isIdenticalTo PMID 25644401
  • isIdenticalTo DOI https://doi.org/10.1186/s12943-015-0287-3
Journal
    • ISSN 1476-4598
    • Molecular Cancer
    14, 19
File
Oaidate2019-10-09T04:24:08Z