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Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0. Epub 2009 Jan 1.

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

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  • 1Terrence Donnelly Heart Centre and Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.

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.

PMID:
19116766
[PubMed - indexed for MEDLINE]
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