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

Angiogenesis
Orisha K YacyshynD J Stewart

Abstract

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

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Citations

Apr 19, 2013·Nature Reviews. Cancer·Suzy V Torti, Frank M Torti
Aug 1, 2013·Journal of the National Cancer Institute·Christopher D Kontos, Christopher G Willett
Sep 3, 2014·The Journal of Clinical Investigation·Jikui ShenPeter A Campochiaro
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Sep 6, 2019·Journal of Diabetes Research·Michael WhiteheadKeith R Martin

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Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

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