Angiogenesis

, Volume 12, Issue 1, pp 25–33 | Cite as

Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells

  • Orisha K. Yacyshyn
  • Patrick F. H. Lai
  • Kelly Forse
  • Krystyna Teichert-Kuliszewska
  • Paul Jurasz
  • Duncan J. Stewart
Original Paper

Abstract

Objectives

The endothelial cell (EC)-selective receptor tyrosine kinase, Tie2, and its ligands angiopoietin Ang-1 and Ang-2, are essential for blood vessel maintenance and repair. Ang-1 is an agonist of Tie2 receptor activation, whereas Ang-2 is a context-dependent antagonist/agonist. Therefore, we investigated the role of the EC-selective phosphatase, human protein tyrosine phosphatase beta (HPTPβ), in regulating Tie2 activity.

Methods and results

siRNA silencing of HPTPβ enhanced Ang-1 and Ang-2-induced Tie2 phosphorylation at 10 min (2.5-fold, < 0.001; and 1.8-fold, < 0.05, respectively). The cell survival response to Ang-1, but not Ang-2, was enhanced by HPTPβ silencing as measured by flow cytometry (0.85-fold to 0.66-fold, < 0.05) and ELISA (0.88-fold to 0.53-fold, < 0.01). Hypoxia, which upregulated HPTPβ expression in endothelial cells, impaired Ang-1-induced Tie2 phosphorylation.

Conclusions

These results reveal a novel role for HPTPβ in modulating Ang-1-Tie2 signaling and endothelial cell survival.

Keywords

Angiogenesis Angiopoietins Apoptosis Endothelial Tie2 receptor Protein tyrosine phosphatase Hypoxia 

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Orisha K. Yacyshyn
    • 1
    • 2
  • Patrick F. H. Lai
    • 1
  • Kelly Forse
    • 3
  • Krystyna Teichert-Kuliszewska
    • 1
  • Paul Jurasz
    • 1
  • Duncan J. Stewart
    • 1
    • 4
  1. 1.Terrence Donnelly Heart Centre and Division of CardiologySt Michael’s HospitalTorontoCanada
  2. 2.Department of PhysiologyUniversity of TorontoTorontoCanada
  3. 3.Human Biology ProgramUniversity of TorontoTorontoCanada
  4. 4.Ottawa Health Research Institute, The Ottawa Hospital Civic CampusUniversity of OttawaOttawaCanada

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