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


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.
Yacyshyn
Orisha K
OK
Terrence Donnelly Heart Centre and Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
Lai
Patrick F H
PF
Forse
Kelly
K
Teichert-Kuliszewska
Krystyna
K
Jurasz
Paul
P
Stewart
Duncan J
DJ
D042683:Angiopoietin-1 / Q000494:pharmacology; D042702:Angiopoietin-2 / Q000494:pharmacology; D042682:Angiopoietins / Q000378:metabolism* / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014638:Vanadates; D042787:Receptor, TIE-2; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5