The Experts below are selected from a list of 61323 Experts worldwide ranked by ideXlab platform
Bernard Degryse - One of the best experts on this subject based on the ideXlab platform.
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In silico docking of Urokinase plasminogen activator and integrins.
BMC bioinformatics, 2008Co-Authors: Bernard Degryse, Juan Fernandez-recio, Valentina Citro, Francescol Blasi, Maria Vittoria CubellisAbstract:Urokinase, its receptor and the integrins are functionally associated and involved in regulation of cell signaling, migration, adhesion and proliferation. No structural information is available on this potential multimolecular complex. However, the tri-dimensional structure of Urokinase, Urokinase receptor and integrins is known. We have modeled the interaction of Urokinase on two integrins, alphaIIbbeta3 in the open configuration and alphavbeta3 in the closed configuration. We have found that multiple lowest energy solutions point to an interaction of the kringle domain of uPA at the boundary between alpha and beta chains on the surface of the integrins. This region is not far away from peptides that have been previously shown to have a biological role in Urokinase receptor/integrins dependent signaling. We demonstrated that in silico docking experiments can be successfully carried out to identify the binding mode of the kringle domain of Urokinase on the scaffold of integrins in the open and closed conformation. Importantly we found that the binding mode was the same on different integrins and in both configurations. To get a molecular view of the system is a prerequisite to unravel the complex protein-protein interactions underlying Urokinase/Urokinase receptor/integrin mediated cell motility, adhesion and proliferation and to design rational in vitro experiments.
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Urokinase Urokinase receptor and vitronectin αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways
Oncogene, 2001Co-Authors: Bernard Degryse, Simone Orlando, Massimo Resnati, Shafaat A Rabbani, Francesco BlasiAbstract:Urokinase/Urokinase receptor and vitronectin/α v β 3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways
Harold A. Chapman - One of the best experts on this subject based on the ideXlab platform.
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identification of the Urokinase receptor as an adhesion receptor for vitronectin
Journal of Biological Chemistry, 1994Co-Authors: Robert J. Drummond, Steven Rosenberg, Harold A. ChapmanAbstract:Abstract Urokinase receptors, expressed on surfaces of many cell types, focus to the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. We now report that the Urokinase receptor (uPAR) is also a high affinity (Kd < 30 nM) receptor for vitronectin. Recombinant uPAR binds vitronectin in the absence of Urokinase, but vitronectin binding is promoted by concurrent receptor binding of either Urokinase or fragments thereof containing its uPAR binding domain. Stable epithelial cell transfectants expressing membrane-anchored uPAR, but not cells expressing soluble uPAR, become strongly adhesive with altered morphology in the absence of Urokinase. These observations identify a new class of vitronectin receptor and imply a duality in function for the receptor that intrinsically links matrix adhesion to regulation of protease activity. Increases in Urokinase receptor expression known to be associated with cellular activation and malignant transformation could modulate cellular trafficking and function by promoting attachment to vitronectin.
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reversible cellular adhesion to vitronectin linked to Urokinase receptor occupancy
Journal of Biological Chemistry, 1994Co-Authors: David A Waltz, Harold A. ChapmanAbstract:Abstract Urokinase receptors are distributed on surfaces of many cell types where they are thought to focus plasminogen-dependent proteolysis important to migration and tissue remodeling to the immediate pericellular space. In addition to its well characterized role in proteolysis, Urokinase receptor binding per se promotes the adhesiveness of leukemic cell lines exposed to differentiating cytokines in vitro. We sought to determine if a serum or matrix component is involved in Urokinase-dependent adhesion. We now report that cytokine-stimulated human myelomonocytic cells express a divalent cation- and Arg-Gly-Asp-independent high affinity receptor for urea-purified vitronectin (Kd < 10 nM). Soluble native vitronectin does not effectively bind to the receptor, while cellular adhesion was noted to both urea-purified and native vitronectin when adsorbed to plastic. The activity of this receptor is tightly coupled to Urokinase receptor occupancy. Urokinase receptor binding thus induces selective and reversible cellular adhesion to the matrix form of vitronectin. Because transfer of vitronectin-bound plasminogen activator inhibitor type 1 to Urokinase promotes rapid turnover of receptor-bound enzyme, these results illuminate a novel binding cycle by which Urokinase receptor occupancy coordinately regulates cellular adhesiveness and pericellular proteolysis.
Francesco Blasi - One of the best experts on this subject based on the ideXlab platform.
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Urokinase Urokinase receptor and vitronectin αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways
Oncogene, 2001Co-Authors: Bernard Degryse, Simone Orlando, Massimo Resnati, Shafaat A Rabbani, Francesco BlasiAbstract:Urokinase/Urokinase receptor and vitronectin/α v β 3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways
Steven Idell - One of the best experts on this subject based on the ideXlab platform.
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Post-transcriptional regulation of Urokinase mRNA. Identification of a novel Urokinase mRNA-binding protein in human lung epithelial cells in vitro.
The Journal of biological chemistry, 2000Co-Authors: Sreerama Shetty, Steven IdellAbstract:Abstract We sought to determine if Urokinase expression is regulated at the post-transcriptional level in cultured lung epithelial cells. We also sought to determine if differences in Urokinase expression by cultured human lung carcinoma and non-malignant lung epithelial subtypes were attributable to post-transcriptional regulatory mechanisms. Urokinase was expressed by phenotypically diverse lung carcinoma cell lines as well as non-malignant small airway epithelial cells and bronchial epithelial cells. Using gel mobility shift and UV cross-linking assays, we identified a 30-kDa Urokinase mRNA-binding protein that selectively bound to a 66-nucleotide protein-binding fragment of Urokinase mRNA. The Urokinase mRNA-binding protein is found in the cytosolic but not nuclear extracts of non-malignant lung epithelial cells; whereas, it is found in the nuclear but not cytosolic extracts of selected malignant carcinoma-derived cells that express relatively large amounts of Urokinase. Chimeric β-globin/Urokinase cDNA containing the Urokinase mRNA-binding protein binding sequence destabilized otherwise stable β-globin mRNA. Our results demonstrate that Urokinase gene expression in lung epithelial and lung carcinoma-derived cells is regulated at the post-transcriptional level. The mechanism involves an interaction between a 66-nucleotide sequence of the Urokinase mRNA 3′-untranslated region with a newly recognized Urokinase mRNA-binding protein to regulate Urokinase mRNA stability.
Choon Sik Yoon - One of the best experts on this subject based on the ideXlab platform.
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Mechanical Thrombectomy of Acute Iliofemoral Deep Vein Thrombosis with Use of an Arrow-Trerotola Percutaneous Thrombectomy Device
Journal of Vascular and Interventional Radiology, 2006Co-Authors: Choon Sik YoonAbstract:PURPOSE To evaluate the immediate and 1-year clinical outcomes of mechanical thrombectomy with use of the Arrow-Trerotola percutaneous thrombectomy device (PTD) with or without low-dose Urokinase in the treatment of acute iliofemoral deep vein thrombosis (DVT) MATERIALS AND METHODS Mechanical thrombectomy with the PTD was performed in 25 patients with acute iliofemoral DVT. Thrombolytic therapy with low-dose Urokinase was used in all patients without contraindications ( n = 20). Other therapies used in combination included inferior vena cava filter insertion ( n = 5), sheath aspiration thrombectomy ( n = 25), and angioplasty and stent placement ( n = 20) RESULTS Initial technical and clinical success was achieved in all cases. In the 20 patients who had no contraindications to the use of Urokinase, the dosage of Urokinase did not exceed 1 million IU (range, 360,000–1,000,000 IU; mean, 640,000 IU). The mean time of Urokinase infusion was 16 hours (range, 12–20). In five patients who had a contraindication to the use of Urokinase, mechanical thrombectomy with the PTD was successful without the use of Urokinase. There were no major complications. Primary patency of the stent-implanted common iliac vein segment was achieved at 1 year in 17 of 20 patients (85%). The overall 1-year clinical success rate was 92% (23 of 25 patients). Valvular insufficiency occurred in two patients (8%) CONCLUSION The PTD is an effective mechanical thrombectomy device in the treatment of acute iliofemoral DVT with or without adjunctive Urokinase thrombolysis
