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evolution
the enzyme belongs to the trypsin superfamily of enzymes
evolution
biochemical and structural analyses suggest that plasminogen activators coevolved with their cognate protein substrates and inhibitors. The binding interfaces of uPA:plasminogen and uPA:PAI-1 may have coevolved to maintain tight interactions
malfunction
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a wide variety of disorders are associated with an imbalance in the plasminogen activator system, including inflammatory diseases, atherosclerosis, intimal hyperplasia, the response mechanism to vascular injury, and restenosis. uPA is implicated in the stimulation of angiogenesis, detailed overview
malfunction
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a wide variety of disorders are associated with an imbalance in the plasminogen activator system, including inflammatory diseases, atherosclerosis, intimal hyperplasia, the response mechanism to vascular injury, and restenosis. uPA is implicated in the stimulation of angiogenesis, detailed overview
malfunction
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a wide variety of disorders are associated with an imbalance in the plasminogen activator system, including inflammatory diseases, atherosclerosis, intimal hyperplasia, the response mechanism to vascular injury, and restenosis. uPA is implicated in the stimulation of angiogenesis, detailed overview
malfunction
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binding of urokinase-type plasminogen activator, uPA, to the uPA receptor, uPAR, existing on the surface of cancer cell is considered to be a trigger for cancer invasions
malfunction
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excessive fibrinolysis in monoclonal antibody light chain-amyloidosis is induced by urokinae-type plasminogen activator from bone marrow plasma cells, uPA expression analysis, overview
malfunction
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inhibition of u-PAR and u-PA attenuates lipopolysaccharid-mediated tumour cell adhesion and invasion
malfunction
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overexpression of uPAR promotes the invasive migration of hair follicle into the dermis in an uPA-dependent and an uPA-independent, ERK-dependent manner during human prenatal development
malfunction
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pancreatic ductal adenocarcinoma, PDAC, expresses high levels of urokinase-type plasminogen activator, its receptor uPAR, and plasminogen activator inhibitor-2, which may play an important role in PDAC progression. Proliferation and migration of pancreatic adenocarcinoma cells via regulation of ERK/p38 signaling is inhibited by suppression of urokinase plasminogen activator receptor. Effects of uPAR in the uPA system on cancer cell development and progression, overview
malfunction
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the urokinase plasminogen activating system is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers
malfunction
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uPA is an important protease believed responsible for several tumour characteristics through its activation of certain proteases and growth factors. uPA is essential in the degradation of peritumour extracellular matrix. uPA, induced by PGE2 from stromal fibroblasts surrounding lung tumour, thus appears to play an important role through EP receptors
malfunction
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uPA is involved in adhesion, migration and invasion of hepatic Hep-G2 cancer cells, inhibition and downregulation of uPA by plumbagin also leads to inhibition of adhesion, migration and invasion by plumbagin in HepG2 cells, overview
malfunction
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uPA is involved in cell invasion of breast cancer cells, uPA is a key regulator of breast cancer invasion and metastasis, overview
malfunction
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uPA overexpression in brain cortex and hippocampus is involved in epileptic pathology
malfunction
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uPA stimulates glioblastoma multiforme cell invasiveness, in sphingosine-1-phosphate-induced invasion using a spheroid invasion assay
malfunction
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uPA transcription and activity is only markedly increased during chronic neurodegeneration, not during acute intracerebral lipopolysaccharide-induced or acute kainate-induced neurodegeneration. Increase in total plasminogen activation with progression of prion disease is apparent in both soluble and membrane fractions
malfunction
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uPA-dependent cleavage of alpha6integrin is involved in onset and progression of osseous metastases. Alpha6 integrin cleavage permits extravasation of human prostate cancer cells from circulation to bone and can be manipulated to prevent metastasis
malfunction
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upregulation of the uPA system is correlated with malignancy of various carcinomas
malfunction
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urokinase plasminogen activator is related to tumor metastasis
malfunction
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urokinase plasminogen activator mediates impairment of hypercapnic and hypotensive cerebrovasodilation and pial artery dilation after cerebral hypoxia/ischemia, which is prevented by inhibition of integrin alphanubeta3, overview. Inhibition of uPA and integrin signaling may preserve cerebrohemodynamic control after hypoxia/ischemia
malfunction
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urokinase plasminogen activator receptor, uPAR, deficient mice show reduced neutrophil recruitment and less severe lung injury during hyperoxia compared to wild-type mice, uPAR deficiency diminishes KC and IL-6 release and enhances activation of pulmonary coagulation, overview
malfunction
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urokinase-type plasminogen activator receptor, u-PAR, is overexpressed in many human malignant tumors including oral squamous cell carcinoma and plays an important role in a variety of cancer key cellular events as a versatile signaling orchestrator. MMP-9, MMP-2 and u-PA enzymatic activities are significantly reduced in u-PAR-specific siRNA cells. RNAi targeting u-PAR can effectively inhibit the metastasis and progression of oral squamous cell carcinoma in vivo
malfunction
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at pathophysiological concentrations above 20 nM, uPA inhibits contractility and increases vascular permeability
malfunction
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livers of uPA-ablated mice elevated TIMP-1 levels do not trigger HGF signalling and do not promote metastasis of a murine T-lymphoma cell line, decreased TIMP-1-induced tumour cell scattering in uPA knockout mice. In contrast, lack of tumour cell-derived uPA induced by gene silencing do not interfere with this pro-metastatic pathway
malfunction
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macrophage-specific uPA overexpression accelerates atherosclerosis and causes aortic root dilation in fat-fed Ldlr-/-mice. Macrophage-expressed uPA accelerates atherosclerosis by stimulation of lesion progression rather than initiation and causes disproportionate lipid accumulation in early lesions. uPA-accelerated atherosclerosis and aortic dilation are largely, if not completely, independent of uPA receptor, uPAR. In the absence of uPA overexpression, however, uPAR contributes modestly to both atherosclerosis and aortic dilation
malfunction
both C57/black 6J, and AlbPLG1 mice expressing the human plasminogen transgene, are significantly more susceptible to invasive Group A Streptococcus strain 5448 disease than enzyme-deficient uPA-/- mice. The observed decrease in virulence in uPA-/- mice correlates directly with a decrease in bacterial dissemination and reduced cell surface plasmin accumulation by Group A Streptococci
malfunction
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enzyme receptor defciient mice show no lipid droplets in their livers compared to wild-type C57BL/6 mice and the triglyceride levels are significantly lower, phenotype, overview
malfunction
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genetic deficiency of enzyme or urokinase plasminogen activator receptor abrogates functional recovery after acute ischemic stroke
malfunction
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in enzyme knockout mice, the number of peritoneal macrophages is lower by 30% than the peritoneal macrophages harvested from wild-type C57BL/6 mice
malfunction
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macrophage adhesion to vitronectin is blocked by plasminogen activator inhibitor-1, which is also able to enhance in turn the two-dimensional migration on this matrix protein
malfunction
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overexpression of urokinase plasminogen activator in macrophages induces spontaneous macrophage accumulation and fibrosis specific to the heart in mice
malfunction
suppression of uPA retards development of pancreatic cancer in nude mice and increases sensitization to gemcitabine
malfunction
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macrophage-specific uPA overexpression accelerates atherosclerosis and causes aortic root dilation in fat-fed Ldlr-/-mice. Macrophage-expressed uPA accelerates atherosclerosis by stimulation of lesion progression rather than initiation and causes disproportionate lipid accumulation in early lesions. uPA-accelerated atherosclerosis and aortic dilation are largely, if not completely, independent of uPA receptor, uPAR. In the absence of uPA overexpression, however, uPAR contributes modestly to both atherosclerosis and aortic dilation
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malfunction
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in enzyme knockout mice, the number of peritoneal macrophages is lower by 30% than the peritoneal macrophages harvested from wild-type C57BL/6 mice
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malfunction
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enzyme receptor defciient mice show no lipid droplets in their livers compared to wild-type C57BL/6 mice and the triglyceride levels are significantly lower, phenotype, overview
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malfunction
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macrophage adhesion to vitronectin is blocked by plasminogen activator inhibitor-1, which is also able to enhance in turn the two-dimensional migration on this matrix protein
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malfunction
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urokinase plasminogen activator receptor, uPAR, deficient mice show reduced neutrophil recruitment and less severe lung injury during hyperoxia compared to wild-type mice, uPAR deficiency diminishes KC and IL-6 release and enhances activation of pulmonary coagulation, overview
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malfunction
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uPA transcription and activity is only markedly increased during chronic neurodegeneration, not during acute intracerebral lipopolysaccharide-induced or acute kainate-induced neurodegeneration. Increase in total plasminogen activation with progression of prion disease is apparent in both soluble and membrane fractions
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malfunction
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genetic deficiency of enzyme or urokinase plasminogen activator receptor abrogates functional recovery after acute ischemic stroke
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metabolism
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involvement of the uPAR/uPA system in CNS function and pathology, overview
metabolism
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NFkappaB-dependent regulation of urokinase plasminogen activator
metabolism
a poor prognosis of pancreatic ductal adenocarcinoma is correlated with increased expression of urokinase plasminogen activator
metabolism
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the enzyme uPA is a serine protease, and together with its membraneassociated receptor uPAR, is part of the uPA/uPAR system, which is an important component of the fibrinolytic system
metabolism
the urokinase plasminogen activation pathways are comprised of urokinase-type plasminogen activator, its plasmalemmal receptor, and extracellular plasminogen
metabolism
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involvement of the uPAR/uPA system in CNS function and pathology, overview
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physiological function
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the plasminogen system plays a crucial role in the repair of a variety of tissues, including skeletal muscle. uPA promotes muscle regeneration by activating hepatocyte growth factor, which, in turn, stimulates proliferation of myoblasts required for regeneration. uPA promotes myoblast proliferation in vitro through its proteolytic activity
physiological function
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the uPA-uPA receptor, uPAR, system plays a critical role in the regulation of cancer cell migration, extracellular matrix invasion, and metastasis. uPA binds with high affinity to a cell surface uPAR, that is a heavily glycosylated glycosylphosphatidylinositol-anchored protein formed by three cysteine-rich LY6-like extracellular domains. uPA-uPAR promotes extracellular proteolysis by regulating plasminogen activation, uPA-uPAR regulates cell-extracellular matrix interactions as an adhesion receptor for vitronectin and through its capacity to modulate integrin function, and uPA-uPAR regulates cell migration as a signal transduction molecule and by its intrinsic chemotactic activity. Src/MAP kinase, but not FAK and PI3K, is involved in ECRG2-regulated, uPA-dependent cell migration/invasion
physiological function
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the urokinase plasminogen activator, uPA, system, comprising of uPA, its receptor uPAR and inhibitor, type 1 plasminogen activator inhibitor, PAI-1, plays a vital role in various biological processes involving extracellular proteolysis, fibrinolysis, cell migration and proliferation
physiological function
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uPA binds to the urokinase receptor, uPAR, expressed on the surface of many cell types, that coordinates plasmin-mediated cell surface proteolysis for matrix remodeling and promotes cell adhesion by acting as a binding protein for vitronectin. Role of uPAR in the phagocytosis of apoptotic cells, a process termed efferocytosis, overview
physiological function
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uPA elicits various cellular responses, involving the activation of distinct signaling pathways
physiological function
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uPA is a multifunctional protein that in addition to its fibrinolytic and matrix degradation capabilities also affects growth factor bioavailability, cytokine modulation, receptor shedding, cell migration and proliferation, phenotypic modulation, protein expression, and cascade activation of proteases, inhibitors, receptors, and modulators. uPA is the crucial protein for neointimal growth and vascular remodeling. Mechanism of fibroblast-to-myofibroblast transformation induced by uPA. Detailed overview
physiological function
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uPA is a multifunctional protein that in addition to its fibrinolytic and matrix degradation capabilities also affects growth factor bioavailability, cytokine modulation, receptor shedding, cell migration and proliferation, phenotypic modulation, protein expression, and cascade activation of proteases, inhibitors, receptors, and modulators. uPA is the crucial protein for neointimal growth and vascular remodeling. Mechanism of fibroblast-to-myofibroblast transformation induced by uPA. Detailed overview
physiological function
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uPA is a multifunctional protein that in addition to its fibrinolytic and matrix degradation capabilities also affects growth factor bioavailability, cytokine modulation, receptor shedding, cell migration and proliferation, phenotypic modulation, protein expression, and cascade activation of proteases, inhibitors, receptors, and modulators. uPA is the crucial protein for neointimal growth and vascular remodeling. Mechanism of fibroblast-to-myofibroblast transformation induced by uPA. Detailed overview
physiological function
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uPA is a potent catalyst of extracellular proteolysis and manifests this action through the conversion of plasminogen into plasmin, which has a range of specificities
physiological function
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uPA is an important activator of fibrinolytic system
physiological function
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urokinase plasminogen activator receptor, u-PAR, binds u-PA and participates in plasminogen activation in addition to modulating several cellular processes such as adhesion, proliferation, and migration
physiological function
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urokinase-type plasminogen activator induces BV-2 microglial cell migration through activation of matrix metalloproteinase-9
physiological function
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plasmin and urokinase-type plasminogen activator are ubiquitous proteases that regulate the extracellular environment and activate each other through proteolytic cleavage. Although neither plasmin nor urokinase-type plasminogen activator exhibit allosteric cooperativity, modeling shows that cooperativity occurs at the system level because of substrate competition, computational simulations and bifurcation analysis, overview. Ultrasensitive, bistable activation of UPA-PLS is possible in the presence of substrate competition
physiological function
plasminogen activator, together with urokinase-type plasminogen activator inhibitor-1, PAI-1, plays a pivotal role in fibrinolysis, cell migration, and tissue remodeling
physiological function
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the urokinase plasminogen activator system is implicated in cell migration and cancer metastasis
physiological function
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the urokinase plasminogen activator/uPA receptor/plasminogen system is involved in the development of atherosclerosis and aneurysms, modeling, overview
physiological function
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two-chain active uPA and uPA-PAI-1 enzyme-inhibitor complex induce phosphorylation of endothelial NOS-Ser1177 in pulmonary microvascular endothelial cells, which is followed by generation of NO and the nitrosylation and dissociation of beta-catenin from VE-cadherin, mechanism of uPA-induced pulmonary vascular permeability in vivo, overview. Effects of uPA-PAI-1 are abrogated by the nitric-oxide synthase inhibitor N-D-nitro-L-arginine methyl ester. The PI3K/Akt pathway is not essential for uPA-induced phosphorylation of eNOS
physiological function
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uPA is a crucial protagonist for the tissue inhibitor of metalloproteinases-1, TIMP-1, induced modulation of a pro-metastatic microenvironment in the liver of mice. Elevated levels of TIMP-1 render the liver more susceptible to metastasis by triggering urokinase plasminogen activator expression as well as hepatocyte growth factor signalling, thereby leading to the fatal scattered infiltration of metastasizing tumour cells throughout the parenchyma of the target organ. Host uPA is necessary for the recruitment of neutrophilic granulocytes and the associated increase of HGF in livers with elevated TIMP-1 levels
physiological function
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uPA is a crucial protagonist for the tissue inhibitor of metalloproteinases-1, TIMP-1, induced modulation of a pro-metastatic microenvironment in the liver of mice. Elevated levels of TIMP-1 render the liver more susceptible to metastasis by triggering urokinase plasminogen activator expression as well as hepatocyte growth factor signalling, thereby leading to the fatal scattered infiltration of metastasizing tumour cells throughout the parenchyma of the target organ. Host uPA is necessary for the recruitment of neutrophilic granulocytes and the associated increase of HGF in livers with elevated TIMP-1 levels
physiological function
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uPA limits the accretion of fibrin after lung injury. uPA regulates the in vitro pulmonary arterial contractility induced by phenylephrine in a dose-dependent manner through two receptor-dependent pathways, and regulates vascular contractility and permeability in vivo. Physiological concentrations of uPA below 1 nM stimulate the contractility of pulmonary arterial rings induced by phenylephrine through the low-density lipoprotein receptor-related protein receptor. The pro-contractile effect of uPA is independent of its catalytic activity. The inhibition of vascular contractility and increase of vascular permeability is mediated through a two-step process that involves docking to N-methyl-Daspartate receptor-1 on pulmonary vascular smooth muscle cells, and requires catalytic activity
physiological function
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urokinase plasminogen activator inhibits HIV virion release from macrophage-differentiated chronically infected cells via activation of RhoA and PKCepsilon. Interaction of urokinase-type plasminogen activator with its cell surface receptor favours virion accumulation in such subcellular compartment in primary monocyte-derived macrophages and chronically infected promonocytic U1 cells differentiated into macrophage-like cells by stimulation with phorbol myristate acetate, PMA, uPA induces actin rearrangement in PMA stimulated U1 cells. uPA/uPAR interaction leads to the redirection of virion accumulation in intra-cytoplasmic vesicles. Anti-HIV effect of uPA is mediated by RhoA and PKCepsilon, but not by PKCdelta. uPA induces activation of RhoA, and of PKC epsilon and delta isoforms
physiological function
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urokinase-type plasminogen activator is a protease involved in tissue remodeling and cell migration, increased expression of uPA in pterygium may covert plasminogen to plasmin, degrade extracellular matrixes, stimulate cell migration, induce angiogenesis, and plays an important role in the development and progression of pterygium
physiological function
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urokinase-type plasminogen activator is involved in diverse physiologic and pathophysiologic processes, including fibrinolysis, cell migration and adhesion, and inflammation, thereby playing a role in efferocytosis. uPA inhibits the uptake of apoptotic neutrophils, suggest a novel mechanism by which elevated levels of uPA may participate in enhancing the duration and severity of inflammatory processes, such as acute lung injury. The phagocytosis of apoptotic neutrophils by macrophages is significantly inhibited by uPA, the process requires the kringle domain of uPA, and involves alphaVbeta3 integrin and vitronectin. But protease activity is not required for uPA to inhibit the engulfment of apoptotic neutrophils by macrophages, overview. Wild-type and inactive uPA are able to inhibit phagocytosis of apoptotic neutrophils by macrophages
physiological function
activated extracellular enzyme cleaves plasminogen to plasmin, which initiates an extracellular protease cascade to degrade the extracellular matrix and facilitate cellular processes such as cellular migration, angiogenesis, tissue remodeling, and wound repair
physiological function
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activation of alphabetagamma-epithelial sodium channel specifically by the enzyme may contribute to fluid clearance under physiological conditions and in injured tissues, multifaceted mechanisms for enzyme-mediated up-regulation of the epithelial sodium channel, which form the cellular and molecular rational for the beneficial effects of urokinase in mitigating mortal pulmonary edema and pleural effusions, overview
physiological function
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increasing concentrations of the enzyme dose-dependently decrease SR-BI protein expression in the liver and Huh-7 hepatoma cell line..The enzyme decreases both the cellular binding of HDL to Huh-7 hepatocytes, and the selective uptake of HDL-cholesteryl ester from HDL, it decreases the removal of HDL-cholesteryl ester in the liver via suppression of the hepatic SR-BI expression
physiological function
role of the enzyme in pancreatic ductal adenocarcinoma cancer stem cells, a large fraction of these side population cells are CD44 and CD24 positive, are gemcitabine resistant, possess sphere-forming ability, and exhibit increased tumorigenicity. The enzyme interacts directly with transcription factors LIM homeobox-2 (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote cancer stemness. The enzyme regulates Lhx2 expression by suppressing expression of miR-124 and p53 expression by repressing its promoter by inactivating HOXA5. Regulation of gene transcription by the enzyme contributes to cancer stemness and clinical lethality
physiological function
the enzyme is primarily involved in cell-associated plasminogen activation. Urokinase-type plasminogen activator contributes to plasmin recruitment and subsequent invasive disease initiation by invasive Group A streptococci in vivo, it hhas a key role in cell surface plasmin acquisition and bacterial dissemination in invasive Group A streptococcus disease
physiological function
the enzyme mediates interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration without affecting matrix metalloproteinase expression, detailed overview. Interleukin-17 increases peripheral blood mesenchymal stem cell adhesion to endothelial cells and transendothelial migration, as well as increases the capacity of cell adhesion to fibronectin, in an urokinase-tyype plasminogen activator-dependent fashion
physiological function
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the enzyme modulates monocyte-to-macrophage differentiation and prevents oxidized LDL-induced macrophage apoptosis via ERK1/2 activation-dependent Bim downregulation, mechanism, overview. Monocyte-to-macrophage differentiation and macrophage death play a pivotal role in atherogenesis. The enzyme and its receptor uPAR are expressed in atherosclerotic lesion macrophages and contribute to atherosclerosis progression
physiological function
the enzyme modulates monocyte-to-macrophage differentiation and prevents oxidized LDL-induced macrophage apoptosis via ERK1/2 activation-dependent Bim downregulation, mechanism, overview. The enzyme attenuates MonoMac6 macrophage-like cell line apoptosis (with maximal inhibition of 51% by 5 nmol/l of enzyme) induced by oxidized LDL and by thapsigargin (inhibitor of sarcoendoplasmic reticulum Ca2þ-ATPase), but not by staurosporine (protein kinase inhibitor), suggesting that the enzyme's antiapoptotic activity is Ca2+-independent, but involves a kinase activation. Monocyte-to-macrophage differentiation and macrophage death play a pivotal role in atherogenesis. The enzyme and its receptor uPAR are expressed in atherosclerotic lesion macrophages and contribute to atherosclerosis progression. The enzyme attenuates endoplasmatic reticulum stress-induced cell death, overview
physiological function
the enzyme plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis
physiological function
the urokinase-type plasminogen activator regulates gene expression in the liver involving peroxisome-proliferator-activated receptor gamma's transcriptional activity and stimulates triglyceride synthesis in Huh-7 hepatoma cells via p38-dependent upregulation of diglyceride acyltransferase 2. Also, the amount of free fatty acids is highly up regulated by the enzyme through activation of the transcription factor SREBP-1., overview
physiological function
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urokinase plasminogen activator and its receptor coordinate a plasmin-mediated proteolytic cascade that is implicated in cell adhesion, cell motility, and matrix breakdown, for example, during inflammation. The enzyme is a central regulator of macrophage three-dimensional invasion, matrix degradation, and adhesion. Macrophage adhesion to vitronectin is enhanced by the enzyme. The enzyme's proteolytic activity is required for optimal macrophage three-dimensional invasion through a matrix barrier
physiological function
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urokinase plasminogen activator induces pro-fibrotic/m2 phenotype in murine cardiac macrophages, overview. The phenotype is adopted after migration of the macrophages to the heart. Elevation of the pro-inflammatory cytokine interleukin-6 in hearts of transgenic mice overexpressing the enzyme, interleukin-6 is not a major effector of the enzyme-induced cardiac fibrosis
physiological function
urokinase-type plasminogen activator is a serine protease that is implicated as a key mediator of cellular invasion and tissue remodeling, the enzyme is thought to play a central role in tumor metastasis and angiogenesis
physiological function
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urokinase-type plasminogen activator is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor and promotes dendritic spine recovery and improves neurological outcome following ischemic stroke. The enzyme does not have an effect on ischemia- or hypoxia-induced neuronal death. The excitotoxic injury induces the clustering of enzyme receptor in dendritic varicosities, and the binding of the enzyme and its receptor promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from enzyme receptor-enriched varicosities mediated by Rac-regulated profilin expression and cofilin phosphorylation
physiological function
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urokinase-type plasminogen activator is involved in diverse physiologic and pathophysiologic processes, including fibrinolysis, cell migration and adhesion, and inflammation, thereby playing a role in efferocytosis. uPA inhibits the uptake of apoptotic neutrophils, suggest a novel mechanism by which elevated levels of uPA may participate in enhancing the duration and severity of inflammatory processes, such as acute lung injury. The phagocytosis of apoptotic neutrophils by macrophages is significantly inhibited by uPA, the process requires the kringle domain of uPA, and involves alphaVbeta3 integrin and vitronectin. But protease activity is not required for uPA to inhibit the engulfment of apoptotic neutrophils by macrophages, overview. Wild-type and inactive uPA are able to inhibit phagocytosis of apoptotic neutrophils by macrophages
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physiological function
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the urokinase plasminogen activator/uPA receptor/plasminogen system is involved in the development of atherosclerosis and aneurysms, modeling, overview
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physiological function
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the enzyme modulates monocyte-to-macrophage differentiation and prevents oxidized LDL-induced macrophage apoptosis via ERK1/2 activation-dependent Bim downregulation, mechanism, overview. Monocyte-to-macrophage differentiation and macrophage death play a pivotal role in atherogenesis. The enzyme and its receptor uPAR are expressed in atherosclerotic lesion macrophages and contribute to atherosclerosis progression
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physiological function
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urokinase plasminogen activator and its receptor coordinate a plasmin-mediated proteolytic cascade that is implicated in cell adhesion, cell motility, and matrix breakdown, for example, during inflammation. The enzyme is a central regulator of macrophage three-dimensional invasion, matrix degradation, and adhesion. Macrophage adhesion to vitronectin is enhanced by the enzyme. The enzyme's proteolytic activity is required for optimal macrophage three-dimensional invasion through a matrix barrier
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physiological function
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the plasminogen system plays a crucial role in the repair of a variety of tissues, including skeletal muscle. uPA promotes muscle regeneration by activating hepatocyte growth factor, which, in turn, stimulates proliferation of myoblasts required for regeneration. uPA promotes myoblast proliferation in vitro through its proteolytic activity
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physiological function
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urokinase-type plasminogen activator is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor and promotes dendritic spine recovery and improves neurological outcome following ischemic stroke. The enzyme does not have an effect on ischemia- or hypoxia-induced neuronal death. The excitotoxic injury induces the clustering of enzyme receptor in dendritic varicosities, and the binding of the enzyme and its receptor promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from enzyme receptor-enriched varicosities mediated by Rac-regulated profilin expression and cofilin phosphorylation
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additional information
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development of specific monoclonal antibodies against uPA able to detect the enzyme in tumor cell surfaces, overview
additional information
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lipopolysaccharide promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner, overview
additional information
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plasminogen activators are serine proteases that are classified as either urokinase-type PA, uPA, or tissue-type PA, tPA, based on their molecular mass
additional information
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sphingosine kinase is necessary for basal activity of the uPA system and glioma cell invasion, while sphingosine 1-phosphate receptor signaling enhances invasion, partially through uPA and CCN1
additional information
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the expression and release of uPA is under active regulation in BV2 microglial cells
additional information
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uPAR is a key receptor involved in the formation of the serine protease plasmin by interacting with uPA and has been implicated in many physiological processes including proliferation and migration, determination of key regulatory regions and splice variants of UPAR, of multiple forms of uPAR, overview
additional information
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chemotherapy prevents osteosarcoma cell invasion by down-regulation of urokinase plasminogen activity via up-regulation of transcription factor early growth response 1, EGR1, during chemotherapy period, overview
additional information
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concept of the protease web as the complex interplay between proteinases, their inhibitors and effector molecules, overview
additional information
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LasB, a thermolysin-like metalloprotease secreted by Pseudomonas aeruginosa, converts the human uPA zymogen into its active form, processes the uPA receptor, inactivates the plasminogen activator inhibitor 1, and activates pro-matrix metalloproteinase 2
additional information
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there exists a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. The conformation-specific antibodies mAb-112 and mAb-12E6B10 are useful to selectively stain pro-uPA or active uPA on the surface of cultured cells
additional information
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urokinase plasminogen activator is elevated in pathological settings such as acute lung injury, where pulmonary arterial contractility and permeability are disrupted
additional information
highly invasive cancers of breast, brain, prostate and lung notably have increased levels of the enzyme, its receptor uPAR, or an endogenous inhibitor protein PAI-1, which correlate with the propensity of a cancer cell type to invade and to disseminate
additional information
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highly invasive cancers of breast, brain, prostate and lung notably have increased levels of the enzyme, its receptor uPAR, or an endogenous inhibitor protein PAI-1, which correlate with the propensity of a cancer cell type to invade and to disseminate
additional information
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the catalytic activity of serine proteases depends on a salt-bridge between the amino group of residue 16 and the side chain of Asp194. The salt-bridge stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some serine proteases exist in only partially active forms, in which the amino group of residue 16 is exposed to the solvent. Such a partially active state is assumed by a truncated form of the murine urokinase-type plasminogen activator consisting of residues 16-243, allosteric interconversion analysis between partially active states and the fully active state, overview. Both a monoclonal antibody (mU3) and a peptidic inhibitor (mupain-1-16) stabilize the active state
additional information
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the enzyme's catalytic domain comprises residues 159-411
additional information
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the enzyme's catalytic domain comprises residues 159-411
additional information
although the interaction areas between protease-substrate and protease-inhibitor are shared, the two interactions are mechanistically different
additional information
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although the interaction areas between protease-substrate and protease-inhibitor are shared, the two interactions are mechanistically different