Back

Title
  • en Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor
Creator
    • en Koutsioumpa, Marina
    • en Poimenidi, Evangelia
    • en Pantazaka, Evangelia
    • en Theodoropoulou, Christina
    • en Skoura, Angeliki
    • en Megalooikonomou, Vasileios
    • en Kieffer, Nelly
    • en Courty, Jose
    • en Mizumoto, Shuji
    • en Papadimitriou, Evangelia
Accessrights open access
Rights
Subject
  • Other en Chondroitin sulphate
  • Other en Endothelial cells
  • Other en Migration
  • Other en Pleiotrophin
  • Other en Tyrosine phosphatases
  • Other en Vascular endothelial growth factor
  • NDC 460
Description
  • Abstract en 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.
Publisher en Biomed Central Ltd
Date
    Issued2015-02-03
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/62916
Relation
  • isIdenticalTo DOI https://doi.org/10.1186/s12943-015-0287-3
  • PMID 25644401
Journal
    • PISSN 1476-4598
      • en Molecular Cancer
      • Volume Number14 Page Start19
File
    • fulltext MC14-19.pdf
    • 3.59 MB (application/pdf)
      • Issued2015-02-03
Oaidate 2023-07-26