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

  • Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0.
Orisha K Yacyshyn  1 ,  Patrick F H Lai ,  Kelly Forse ,  Krystyna Teichert-Kuliszewska ,  Paul Jurasz ,  Duncan J Stewart
Affiliations
  • 1. Terrence Donnelly Heart Centre and Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
PMID: 19116766 DOI: 10.1007/s10456-008-9126-0
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 (HPTPbeta), in regulating Tie2 activity.

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

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