ArticleThe Journal of cell biology1991
Thrombin neutralizes plasminogen activator inhibitor 1 (PAI-1) that is complexed with vitronectin in the endothelial cell matrix.
Article in The Journal of cell biology, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 75 citations in OpenAlex.
- Endothelial PAI-1 (Plasminogen Activator Inhibitor-1) Blocks the Intrinsic Pathway of Coagulation, Inducing the Clearance and Degradation of FXIa (Activated Factor XI).Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Promoter hypermethylation and silencing of tissue factor pathway inhibitor-2 in oral squamous cell carcinoma.Journal of translational medicine · 2014Article
- Remarkable stabilization of plasminogen activator inhibitor 1 in a "molecular sandwich" complex.Biochemistry · 2013Article
- Novel aspects of urokinase function in the injured lung: role of α2-macroglobulin.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- The vitronectin-binding domain of plasminogen activator inhibitor-1 plays an important functional role in lipopolysaccharide-induced lethality in mice.Journal of thrombosis and haemostasis : JTH · 2012Article
- Plasminogen activator inhibitor-1 inhibits factor VIIa bound to tissue factor.Journal of thrombosis and haemostasis : JTH · 2011Article
- Antimetastatic potential of PAI-1-specific RNA aptamers.Oligonucleotides · 2009Article
- Article
- The cluster of basic amino acids in vitronectin contributes to its binding of plasminogen activator inhibitor-1: evidence from thrombin-, elastase- and plasmin-cleaved vitronectins and anti-peptide antibodies.The Biochemical journal · 1997Article
- Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis.Proceedings of the National Academy of Sciences of the United States of America · 1992Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitronectin endows plasminogen activator inhibitor 1 (PAI-1), the fast-acting inhibitor of both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), with additional thrombin inhibitory properties. In view of the apparent association between PAI-1 and vitronectin in the endothelial cell matrix (ECM), we analyzed the interaction between PAI-1 and thrombin in this environment. Upon incubating 125I-labeled alpha-thrombin with endothelial cell matrix (ECM), the protease formed SDS-stable complexes exclusively with PAI-1, with subsequent release of these complexes into the supernatant. Vitronectin was required as a cofactor for the association between PAI-1 and thrombin in ECM. Metabolic labeling of endothelial cell proteins, followed by incubation of ECM with t-PA, u-PA, or thrombin, indicated that all three proteases depleted PAI-1 from ECM by complex formation and proteolytic cleavage. Proteolytically inactive thrombin as well as anticoagulant thrombin, i.e., thrombin in complex with its endothelial cell surface receptor thrombomodulin, did not neutralize PAI-1, emphasizing that the procoagulant moiety of thrombin is required for a functional interaction with PAI-1. A physiological implication of our findings may be related to the mutual neutralization of both PAI-1 and thrombin, providing a new link between plasminogen activation and the coagulation system. Evidence is provided that in ECM, procoagulant thrombin may promote plasminogen activator activity by inactivating PAI-1.
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