title: Hypoxia reduces endothelial Ang1-induced Tie2 activity in a Tie1-dependent manner.
abstract: Despite the altered expression of Tie receptors and angiopoietin ligands during hypoxic conditions, the effect of hypoxia on Tie-mediated endothelial responses has not been elucidated. In this study, we found that hypoxia increased Tie receptor expression but attenuated angiopoietin-1 (Ang1)-induced Tie2 activity, including Tie2 phosphorylation, Tie2 downstream signaling activation, and endothelial cell tube formation. However, Ang1 binding to endothelial cells was increased during hypoxic conditions. We demonstrated that Tie1 suppression restored the Tie2 activity and that Tie1-mediated Tie2 suppression was independent of tyrosine phosphatase activity. These results suggest that under hypoxic conditions, Tie1 is critical for reducing Ang1-induced Tie2 activity and angiogenesis.
authors.affiliation: Department of Pharmacology and Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jang-Hyuk
authors.initials: JH
authors.lastname: Yun
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Park
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D042810:Receptor, TIE-1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042810:Receptor, TIE-1
keywords: Ang1; Angiopoietin; DFX; Endothelial proliferation; HIF; HUVEC; Hypoxia; PI3K; Tie1; Tie2; VE-PTP; VEGF; angiopoietin-1; desferrioxamine; human umbilical vein endothelial cell; hypoxia-inducible factor; mTOR; mammalian target of rapamycin; phosphatidylinositol 3-kinase; vascular endothelial growth factor; vascular endothelial protein tyrosine phosphatase