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

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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, 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 HPTPβ 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 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.

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Acknowledgement

This study was supported by a grant from the Canadian Institutes of Health Research (82791), a fellowship from the Heart and Stroke Foundation of Canada to P.J., and a Government of Ontario/Heart and Stroke Foundation of Ontario Graduate Scholarship in Science and Technology to O.K.Y.

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Authors and Affiliations

  1. Terrence Donnelly Heart Centre and Division of Cardiology, St Michael’s Hospital, 30 Bond St., Toronto, ON, M5B 1W8, Canada

    Orisha K. Yacyshyn, Patrick F. H. Lai, Krystyna Teichert-Kuliszewska, Paul Jurasz & Duncan J. Stewart

  2. Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada

    Orisha K. Yacyshyn

  3. Human Biology Program, University of Toronto, Toronto, ON, M5S 1A8, Canada

    Kelly Forse

  4. Ottawa Health Research Institute, The Ottawa Hospital Civic Campus, University of Ottawa, 725 Parkdale Avenue, Ottawa, ON, K1Y 4E9, Canada

    Duncan J. Stewart

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  1. Orisha K. Yacyshyn
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  2. Patrick F. H. Lai
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  3. Kelly Forse
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Correspondence to Duncan J. Stewart.

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Yacyshyn, O.K., Lai, P.F.H., Forse, K. et al. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis 12, 25–33 (2009). https://doi.org/10.1007/s10456-008-9126-0

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  • DOI: https://doi.org/10.1007/s10456-008-9126-0

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