ArticleAmerican journal of physiology. Cell physiology2008
The inhibitory effect of HKa in endothelial cell tube formation is mediated by disrupting the uPA-uPAR complex and inhibiting its signaling and internalization.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
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- Overexpression of the Kininogen-1 inhibits proliferation and induces apoptosis of glioma cells.Journal of experimental & clinical cancer research : CR · 2018Article
- Application of Isobaric Tags for Relative and Absolute Quantification (iTRAQ) Coupled with Two-Dimensional Liquid Chromatography/Tandem Mass Spectrometry in Quantitative Proteomic Analysis for Discovery of Serum Biomarkers for Idiopathic Pulmonary Fibrosis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Identification of Key Genes and Pathways in Tongue Squamous Cell Carcinoma Using Bioinformatics Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Novel role for p56/Lck in regulation of endothelial cell survival and angiogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- The high-molecular-weight kininogen domain 5 is an intrinsically unstructured protein and its interaction with ferritin is metal mediated.Protein science : a publication of the Protein Society · 2014Article
- Domain 2 of uPAR regulates single-chain urokinase-mediated angiogenesis through β1-integrin and VEGFR2.American journal of physiology. Heart and circulatory physiology · 2013Article
- Identification of O-glycosylated proteins that are aberrantly excreted in the urine of patients with early stage ovarian cancer.International journal of molecular sciences · 2013Article
- Identification of kininogen-1 as a serum biomarker for the early detection of advanced colorectal adenoma and colorectal cancer.PloS one · 2013Article
- Article
- Interaction of high-molecular-weight kininogen with endothelial cell binding proteins suPAR, gC1qR and cytokeratin 1 determined by surface plasmon resonance (BiaCore).Thrombosis and haemostasis · 2011Article
- Patients with ovarian carcinoma excrete different altered levels of urine CD59, kininogen-1 and fragments of inter-alpha-trypsin inhibitor heavy chain H4 and albumin.Proteome science · 2010Article
- Article
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5 authors at 1 institution in 1 country.
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Abstract
In two-dimensional (2-D) culture systems, we have previously shown that cleaved two-chain high-molecular-weight kininogen (HKa) or its domain 5 induced apoptosis by disrupting urokinase plasminogen activator (uPA) receptor (uPAR)-integrin signal complex formation. In the present study, we used a three-dimensional (3-D) collagen-fibrinogen culture system to monitor the effects of HKa on tube formation. In a 3-D system, HKa significantly inhibited tube and vacuole formation as low as 10 nM, which represents 1.5% of the physiological concentration of high-molecular-weigh kininogen (660 nM), without apparent apoptosis. However, HKa (300 nM) completely inhibited tube formation and increased apoptotic cells about 2-fold by 20-24 h of incubation. uPA-dependent ERK activation and uPAR internalization regulate cell survival and migration. In a 2-D system, we found that exogenous uPA-induced ERK phosphorylation and uPAR internalization were blocked by HKa. In a 3-D system, we found that not only uPA-uPAR association but also the activation of ERK were inhibited by HKa. HKa disrupts the uPA-uPAR complex, inhibiting the signaling pathways, and also inhibits uPAR internalization and regeneration to the cell surface, thereby interfering with uPAR-mediated cell migration, proliferation, and survival. Thus, our data suggest that the suppression of ERK activation and uPAR internalization by HKa contributes to the inhibition of tube formation. We conclude that in this 3-D collagen-fibrinogen gel, HKa modulates the multiple functions of uPAR in endothelial cell tube formation, a process that is closely related to in vivo angiogenesis.
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