Information on EC 3.4.21.73 - u-Plasminogen activator

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The expected taxonomic range for this enzyme is: Opisthokonta

EC NUMBER
COMMENTARY
3.4.21.73
-
RECOMMENDED NAME
GeneOntology No.
u-Plasminogen activator
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Specific cleavage of Arg-/-Val bond in plasminogen to form plasmin
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Abbokinase
-
-
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-
Cellular plasminogen activator
-
-
-
-
Double-chain urokinase-type plasminogen activator
-
-
-
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Plasminogen activator, urokinase-type
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-
-
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Two-chain urokinase-type plasminogen activator
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-
-
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u-PA
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-
-
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U-plasminogen activator
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-
-
-
uPA
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-
-
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Urinary plasminogen activator
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Urokinase
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-
-
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Urokinase plasminogen activator
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-
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Urokinase-type plasminogen activator
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY
139639-24-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Calbiochem
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Manually annotated by BRENDA team
commercial preparation from Sigma Aldrich
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-
Manually annotated by BRENDA team
commercial preparation of low-molecular weight uPA from American Diagnostica
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-
Manually annotated by BRENDA team
from Sandoz, Nrnberg
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-
Manually annotated by BRENDA team
high-molecular weight uPA expressed in SP2/0 cell culture from Abbott Biotech; low-molecular weight uPA, Abbokinase, from Abbott Labs, North Chicago
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-
Manually annotated by BRENDA team
nonphosphorylated and phosphorylated on serine
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-
Manually annotated by BRENDA team
patients with acute and chronic hepatitis B
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-
Manually annotated by BRENDA team
patients with allergic asthma
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-
Manually annotated by BRENDA team
patients with colorectal cancer
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Manually annotated by BRENDA team
patients with common variable immunodeficiency
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-
Manually annotated by BRENDA team
patients with Quebec platelet disease
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Manually annotated by BRENDA team
recombinant 54000 MW scuPA, plasmin-resistant rscuPA with Lys158 mutagenized to Glu and a 32000 MW form of rscuPA consisting of Leu144-Leu411 are obtained by expression of cDNA in Chinese hamster ovary cells
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-
Manually annotated by BRENDA team
recombinant amino-terminal fragment S1-E143 expressed in Pichia pastoris
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Manually annotated by BRENDA team
recombinant plasmin-resistant mutant of single-chain uPA obtained by site-specific mutagenesis of Lys158 to Glu
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-
Manually annotated by BRENDA team
recombinant single chain urokinase-type plasminogen activator is home-made by expression of uPA cDNA in Chinese hamster ovary cells
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-
Manually annotated by BRENDA team
single chain form
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-
Manually annotated by BRENDA team
single-chain uPA
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-
Manually annotated by BRENDA team
uPA from Serono and low-molecular weight uPa from Le Petit
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-
Manually annotated by BRENDA team
commercial preparation of low-molecular weight uPA from American Diagnostica
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-
Manually annotated by BRENDA team
high-molecular weight uPA expressed in SP2/0 cell culture from Abbott Biotech; low-molecular weight uPA, Abbokinase, from Abbott Labs, North Chicago
-
-
Manually annotated by BRENDA team
recombinant 54000 MW scuPA, plasmin-resistant rscuPA with Lys158 mutagenized to Glu and a 32000 MW form of rscuPA consisting of Leu144-Leu411 are obtained by expression of cDNA in Chinese hamster ovary cells
-
-
Manually annotated by BRENDA team
recombinant single chain urokinase-type plasminogen activator is home-made by expression of uPA cDNA in Chinese hamster ovary cells
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-
Manually annotated by BRENDA team
uPA from Serono and low-molecular weight uPa from Le Petit
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-
Manually annotated by BRENDA team
C57BL/6J mice
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Manually annotated by BRENDA team
mice model for kidney ischemia reperfusion injury and for acute kidney allograft rejection
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-
Manually annotated by BRENDA team
Mus musculus C57BL/6
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-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
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-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
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-
Manually annotated by BRENDA team
piglets
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
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
-
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
-
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
-
inhibition of u-PAR and u-PA attenuates lipopolysaccharid-mediated tumour cell adhesion and invasion
malfunction
-
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
-
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
-
uPA is involved in cell invasion of breast cancer cells, uPA is a key regulator of breast cancer invasion and metastasis, overview
malfunction
-
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
-
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
Mus musculus C57BL/6
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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, 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, 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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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
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
-
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
-
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
-
uPA is an important activator of fibrinolytic system
physiological function
-
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
-
urokinase-type plasminogen activator induces BV-2 microglial cell migration through activation of matrix metalloproteinase-9
physiological function
-
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
-
the urokinase plasminogen activator system is implicated in cell migration and cancer metastasis
physiological function
-
the urokinase plasminogen activator/uPA receptor/plasminogen system is involved in the development of atherosclerosis and aneurysms, modeling, overview
physiological function
-
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 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
-
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
-
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
Mus musculus C57BL/6
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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, the urokinase plasminogen activator/uPA receptor/plasminogen system is involved in the development of atherosclerosis and aneurysms, modeling, overview, 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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metabolism
Mus musculus C57BL/6
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involvement of the uPAR/uPA system in CNS function and pathology, overview
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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
-
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
-
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
-
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha6 integrin + H2O
?
show the reaction diagram
-
alpha6 integrin is present on prostate carcinoma escaping the gland via nerves. Urokinase-dependent cleavage of the laminin binding domain from the prostate tumor cell surface, i.e. alpha6p
-
-
?
benzoyl-beta-Ala-Gly-Arg-4-nitroanilide + H2O
benzoyl-beta-Ala-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Benzyloxycarbonyl-Gly-Gly-Arg-amino-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
-
Cellular receptor of urokinase-type plasminogen activator + H2O
?
show the reaction diagram
-
cleavage between domains 1 and 2 generating a cell-associated variant of the receptor of urokinase-type plasminogen activator without ligand-binding properties, uPA catalyzed cleavage does not require binding of the protease to the receptor through its epidermal growth factor-like receptor-binding domain, low-molecular weight uPA lacking this domain also cleaves the substrate
-
-
-
D-Glu-Gly-Arg-4-nitroanilide + H2O
D-Glu-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
a uPA substrate S-2444
-
-
?
D-Val-Leu-Lys-4-nitroanilide + H2O
D-Val-Leu-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
GSGRSA + H2O
GSGR + Ser-Ala
show the reaction diagram
-
-
-
?
HYGRSA + H2O
HYGR + Ser-Ala
show the reaction diagram
-
-
-
?
Kininogen + H2O
Kinin
show the reaction diagram
-
-
-
-
L-pyroGlu-Gly-L-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
i.e. S-2444
-
-
?
L-pyroGlu-Gly-L-Arg-4-nitroanilide + H2O
?
show the reaction diagram
-
chromogenic substrate S-2444
-
-
?
PFGRSA + H2O
PFGR + Ser-Ala
show the reaction diagram
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
generation of 2 polypeptides, one of 80000 MW (A-chain), and the other of 27000 MW (B-chain)
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
Glu-plasminogen, the native form of human plasminogen
-
-
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
principal function is fibrinolysis, u-PA also been implicated in other physiological functions such as embryogenesis, cell migration, tissue remodeling, ovulation, and wound healing
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
activation
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
hearts with end-stage failure and fibrosis have macrophage accumulation and elevated plasminogen activator activity, mechanisms that link macrophage accumulation and plasminogen activator activity with cardiac fibrosis, dependent on localization of uPA by the uPA receptor uPAR, on activation of plasminogen by uPA and subsequent activation of transforming growth factor-beta1 and matrix metalloproteinase MMP-2 and MMP-9 by plasmin, overview, uPA-induced cardiac fibrosis can be attenuated by treatment with verapamil, plasminogen is necessary for uPA-induced cardiac fibrosis and macrophage accumulation, but uPAR is not
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
the urokinase-type and tissue-type plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen to the active protease plasmin, uPA is bound to its receptor uPAR, overview
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
human Glu-plasminogen
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
human plasminogen
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
the uPA proteolytic domain specifically cleaves plasminogen and converts it into the serine protease plasmin with wide substrate specificity. Plasmin directly degrades fibrin, leading to thrombus dissolution and activating a number of matrix metalloproteinases
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
u-PA forms a complex with its receptor u-PAR in plasminogen ativation
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
uPA needs to be activated
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
casein-plasminogen zymography assay method
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
plasminogen + H2O
?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
?
show the reaction diagram
-
physiological function
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
physiological function
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
physiological function
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
the enzyme mediates pericellular proteolysis during cell migration and tissue remodelling under physiological and pathophysiological conditions
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
potential role for uPA is a direct regulation of metalloproteinases-mediated extracellular proteolysis via the cleavage of the 72000 MW gelatinase/type IV collagenase to an 62000 MW form
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
key enzyme in the thrombolytic cascade converting plasminogen into plasmin, which in turn degrades thrombus fibrin
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
the enzyme promotes fibrinolysis by catalyzing the conversion of plasminogen to plasmin, when localized to the external cell surface it contributes to tissue remodelling and cellular migration
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
the enzyme is responsible for plasminogen activation, it is also involved in cell adhesion, chemotaxis, and proliferation, the signaling events are not mediated by uPA receptor uPAR/CD87, but require the kringle domain of the enzyme, which binds integrin alphanybeta3 for induction of cell migration, e.g. of CHO cells, overview
-
-
?
pro-hepatic growth factor + H2O
mature hepatic growth factor + ?
show the reaction diagram
Mus musculus, Mus musculus C57BL/6
-
uPA activates the hepatic growth factor from its inactive single-chain form to the active alpha-chain form
-
-
?
pyroGlu-Gly-Arg-4-nitroanilide + H2O
pyroGlu-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
i.e. S-2444, a chromogenic substrate
-
-
?
QRGRSA + H2O
QRGR + Ser-Ala
show the reaction diagram
-
-
-
?
S-2444 + H2O
?
show the reaction diagram
-
chromogenic substrate
-
-
?
S-2444 + H2O
?
show the reaction diagram
-
i.e. pyro-Glu-Gly-Arg-p-nitroanilide, a chromogenic substrate
-
-
?
S2444 + H2O
?
show the reaction diagram
-
i.e. 5-oxo-L-Pro-Gly-L-Arg-p-nitroanilide
-
?
t-butyloxycarbonyl-valyl-leucyl-lysine-4-methylcoumaryl-7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
urokinase plasminogen activator receptor + H2O
?
show the reaction diagram
-
receptor cleavage by u-PA, u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases, biological significance, overview, receptor cleavage by u-PA, u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases
-
-
?
YGAKAY + H2O
YGAK + Ala-Tyr
show the reaction diagram
-
-
-
?
Z-RRG-7-amido-4-methylcoumarin + H2O
Z-RRG + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
L-pyroglutamyl-glycyl-L-arginine-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
additional information
?
-
-
binding of single-chain uPA moiety to its substrate plasminogen occurs with lower affinity compared to binding of the two-chain uPA moiety
-
-
-
additional information
?
-
-
disulfide bridges in the catalytic domain are essential for maintaining amidolytic and fibrinolytic activity
-
-
-
additional information
?
-
-
the enzyme cleaves its cellular receptor between domains 1 and 2
-
-
-
additional information
?
-
-
lyses fibrin clots containing plasminogen but not plasminogen-free fibrin
-
-
-
additional information
?
-
-
urokinase-type plasminogen activator includes its single-chain zymogen, pro-urokinase and two-chain enzyme urokinase
-
?
additional information
?
-
-
active enzyme promotes tumor progression, activation of enzyme appears as a key step in tumor progression
-
-
-
additional information
?
-
-
enzyme protein is consistently elevated in the hyperproliferative hair follicle keratinocyte, and inhibiton of enzyme decreases hair follicle keratinocyte proliferation
-
-
-
additional information
?
-
-
enzyme released by alveolar epithelial cells alters alveolar epithelial repair in vitro by modulating the underlying fibrin matrix
-
-
-
additional information
?
-
-
structure and interdomain contacts of the N-terminal domain of the enzyme with the uPA receptor, binding structure, mechanisms responsible for the cellular responses induced by uPA binding, overview
-
-
-
additional information
?
-
-
the enzyme is a serine protease involved in tissue remodeling and cell migration, the active form of uPA is bound to its high affinity receptor on the cell surface, where specific inhibitors modulate its enzymatic activity, such inhibitors also regulate the cell surface levels of uPA by triggering the internalization of the uPA-receptor-inhibitor complex via endocytosis, overview, the C-terminus of the N-terminal region contains a sequence that interacts with alphaVbeta3 integrin and is relevant for cell migration, overview
-
-
-
additional information
?
-
-
the enzyme is involved in colorectal cancer invasion and metastasis
-
-
-
additional information
?
-
-
the enzyme plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis
-
-
-
additional information
?
-
-
the enzyme supports liver repair independent of its cellular receptor uPAR, overview
-
-
-
additional information
?
-
-
the enzyme-plasminogen activator inhibitor-1 complex in intenalized by endocytosis via binding of membrane-bound receptors, overview
-
-
-
additional information
?
-
-
trans-3,4-dimethyl-3-hydroxyflavanone, a hair growth enhancing active component, decreases active transforming growth factor beta2 and the TGF-b 2 activation cascade through control of uPA on the surface of keratinocytes, mechanism, overview
-
-
-
additional information
?
-
-
uPA interacts with the uPA receptor, which is important for many of the enzyme's biological functions
-
-
-
additional information
?
-
-
urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice, depletion of macrophages leads to reduced hypertrophy of muscles, overview
-
-
-
additional information
?
-
-
urokinase-type plasminogen activator plays essential roles in skeletal muscle regeneration and healing, macrophage depletion leads to impaired muscle regeneration, molecular mechanism, overview, the macrophage enzyme is essentially required for chemotaxis, mechanism independent of receptor binding, overview
-
-
-
additional information
?
-
-
recombinant uPA binds purified soluble human integrin alphanybeta3, overview
-
-
-
additional information
?
-
-
structure activity relationship
-
-
-
additional information
?
-
-
the amino-terminal fragment ATF of uPA contains an EGF-like and a kringle domain, involved in the binding of the receptor, chain B contains the catalytic site and maintains the ability to activate plasminogen also when it is not bound to the receptor, the C-terminus of the N-terminal region contains a sequence that interacts with alphaVbeta3 integrin and is relevant for cell migration, overview
-
-
-
additional information
?
-
-
addition of uPA to natural killer cell receptor Ly49E positive adult and fetal natural killer cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively. Effects are dependent on receptor Ly49E
-
-
-
additional information
?
-
-
incubation of macrophages with uPA results in increased expression of paraoxonase 2. The resulting effects such as increase in macrophage oxidative stress, reactive oxygen formation, superoxide anion release, and cell-mediated low-density lipoprotein oxidation cannot be reproduced in macrophages harvested from p47phox-/- mice
-
-
-
additional information
?
-
-
incubation of THP-1 macrophage-like cells with uPA results in increased expression of paraoxonase 2. The effect requires uPA/uPA receptor interaction and is abolished by cell treatment with antioxidants. Presence of uPA increases macrophage oxidative stress, reactive oxygen formation, superoxide anion release, and cell-mediated low-density lipoprotein oxidation. Effects are related to uPA-mediated activation of NADPH oxidase
-
-
-
additional information
?
-
-
induction of endotoxin lipopolysaccharide-mediated uPA receptor expression is mediated through tyrosine phosphorylation of phophoglycerate kinase and heterogenous nuclear ribonucleoprotein C. This involves expression of uPA as an obligate intermediary
-
-
-
additional information
?
-
-
uterine natural killer cells may regulate extravillous trophoblast invasion and spiral artery remodeling via the uPA system
-
-
-
additional information
?
-
-
uPA and uPAderived peptides maintaining an amino-terminal fragment growth factor-like domain, including the so-called Omega loop, but not the enzymatically competent low molecular weight fragment, inhibit HIV expression in chronically infected U1 cells stimulated with either phorbol 12-myristate 13-acetate or tumor necrosis factor alpha. Both uPA receptor siRNA ands soluble anti-beta1/beta2 monomclonal antibodies abolish the anti-HIV effects of uPA
-
-
-
additional information
?
-
-
inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model, overview. The uPA/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors
-
-
-
additional information
?
-
-
uPA forms a complex with its cogante receptor uPAR, specific interctions, analysis, overview
-
-
-
additional information
?
-
-
uPA, uPA receptor, and plasminogen activator inhibitor form the urokinase-type plasminogen activator system
-
-
-
additional information
?
-
-
uPA-uPAR complexes concentrate the plasmin production that provides extracellular matrix proteolysis, weakened cell-cell contact, and increased cell motility. The proteolytic mechanisms include uPA-induced plasmin generation at focal adhesion sites, which results in extracellular matrix degradation and thus facilitates the detachment of the cell's trailing edge. Plasmin inhibitors can suppress cell migration both in vitro, mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury, overview. Urokinase signaling, overview
-
-
-
additional information
?
-
-
urokinase-type plasmin activator, uPA, binding to uPA receptor, uPAR, induces migration/invasion through multiple interactors including integrins, overview. ECRG2 binds specifically to the kringle domain of uPA, and forms a complex with uPA-uPAR, the trinary complex modifies the dynamical association of uPAR with beta1 integrins. Identification of ECRG2-binding sequence in uPA, overview. Complex disruption inhibits the Src/mitogen-activated protein kinase pathway, resulting in suppression of cell migration/invasion
-
-
-
additional information
?
-
-
uPA-induced phosphorylation of endothelial nitric oxide synthase, eNOS, which is inhibited by myristoylated PKI, a protein kinase A inhibitor
-
-
-
additional information
?
-
Mus musculus C57BL/6
-
urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice, depletion of macrophages leads to reduced hypertrophy of muscles, overview
-
-
-
additional information
?
-
Mus musculus C57BL/6
-
urokinase-type plasminogen activator plays essential roles in skeletal muscle regeneration and healing, macrophage depletion leads to impaired muscle regeneration, molecular mechanism, overview, the macrophage enzyme is essentially required for chemotaxis, mechanism independent of receptor binding, overview
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model, overview. The uPA/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
principal function is fibrinolysis, u-PA also been implicated in other physiological functions such as embryogenesis, cell migration, tissue remodeling, ovulation, and wound healing
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
activation
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
hearts with end-stage failure and fibrosis have macrophage accumulation and elevated plasminogen activator activity, mechanisms that link macrophage accumulation and plasminogen activator activity with cardiac fibrosis, dependent on localization of uPA by the uPA receptor uPAR, on activation of plasminogen by uPA and subsequent activation of transforming growth factor-beta1 and matrix metalloproteinase MMP-2 and MMP-9 by plasmin, overview, uPA-induced cardiac fibrosis can be attenuated by treatment with verapamil, plasminogen is necessary for uPA-induced cardiac fibrosis and macrophage accumulation, but uPAR is not
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
the urokinase-type and tissue-type plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen to the active protease plasmin, uPA is bound to its receptor uPAR, overview
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
the uPA proteolytic domain specifically cleaves plasminogen and converts it into the serine protease plasmin with wide substrate specificity. Plasmin directly degrades fibrin, leading to thrombus dissolution and activating a number of matrix metalloproteinases
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
u-PA forms a complex with its receptor u-PAR in plasminogen ativation
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
uPA needs to be activated
-
-
?
plasminogen + H2O
?
show the reaction diagram
-
physiological function
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
physiological function
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
physiological function
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
the enzyme mediates pericellular proteolysis during cell migration and tissue remodelling under physiological and pathophysiological conditions
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
potential role for uPA is a direct regulation of metalloproteinases-mediated extracellular proteolysis via the cleavage of the 72000 MW gelatinase/type IV collagenase to an 62000 MW form
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
key enzyme in the thrombolytic cascade converting plasminogen into plasmin, which in turn degrades thrombus fibrin
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
the enzyme promotes fibrinolysis by catalyzing the conversion of plasminogen to plasmin, when localized to the external cell surface it contributes to tissue remodelling and cellular migration
-
-
-
plasminogen + H2O
?
show the reaction diagram
-
the enzyme is responsible for plasminogen activation, it is also involved in cell adhesion, chemotaxis, and proliferation, the signaling events are not mediated by uPA receptor uPAR/CD87, but require the kringle domain of the enzyme, which binds integrin alphanybeta3 for induction of cell migration, e.g. of CHO cells, overview
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
pro-hepatic growth factor + H2O
mature hepatic growth factor + ?
show the reaction diagram
Mus musculus, Mus musculus C57BL/6
-
uPA activates the hepatic growth factor from its inactive single-chain form to the active alpha-chain form
-
-
?
urokinase plasminogen activator receptor + H2O
?
show the reaction diagram
-
receptor cleavage by u-PA, u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases, biological significance, overview
-
-
?
alpha6 integrin + H2O
?
show the reaction diagram
-
alpha6 integrin is present on prostate carcinoma escaping the gland via nerves. Urokinase-dependent cleavage of the laminin binding domain from the prostate tumor cell surface
-
-
?
additional information
?
-
-
active enzyme promotes tumor progression, activation of enzyme appears as a key step in tumor progression
-
-
-
additional information
?
-
-
enzyme protein is consistently elevated in the hyperproliferative hair follicle keratinocyte, and inhibiton of enzyme decreases hair follicle keratinocyte proliferation
-
-
-
additional information
?
-
-
enzyme released by alveolar epithelial cells alters alveolar epithelial repair in vitro by modulating the underlying fibrin matrix
-
-
-
additional information
?
-
-
structure and interdomain contacts of the N-terminal domain of the enzyme with the uPA receptor, binding structure, mechanisms responsible for the cellular responses induced by uPA binding, overview
-
-
-
additional information
?
-
-
the enzyme is a serine protease involved in tissue remodeling and cell migration, the active form of uPA is bound to its high affinity receptor on the cell surface, where specific inhibitors modulate its enzymatic activity, such inhibitors also regulate the cell surface levels of uPA by triggering the internalization of the uPA-receptor-inhibitor complex via endocytosis, overview, the C-terminus of the N-terminal region contains a sequence that interacts with alphaVbeta3 integrin and is relevant for cell migration, overview
-
-
-
additional information
?
-
-
the enzyme is involved in colorectal cancer invasion and metastasis
-
-
-
additional information
?
-
-
the enzyme plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis
-
-
-
additional information
?
-
-
the enzyme supports liver repair independent of its cellular receptor uPAR, overview
-
-
-
additional information
?
-
-
the enzyme-plasminogen activator inhibitor-1 complex in intenalized by endocytosis via binding of membrane-bound receptors, overview
-
-
-
additional information
?
-
-
trans-3,4-dimethyl-3-hydroxyflavanone, a hair growth enhancing active component, decreases active transforming growth factor beta2 and the TGF-b 2 activation cascade through control of uPA on the surface of keratinocytes, mechanism, overview
-
-
-
additional information
?
-
-
uPA interacts with the uPA receptor, which is important for many of the enzyme's biological functions
-
-
-
additional information
?
-
-
urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice, depletion of macrophages leads to reduced hypertrophy of muscles, overview
-
-
-
additional information
?
-
-
urokinase-type plasminogen activator plays essential roles in skeletal muscle regeneration and healing, macrophage depletion leads to impaired muscle regeneration, molecular mechanism, overview, the macrophage enzyme is essentially required for chemotaxis, mechanism independent of receptor binding, overview
-
-
-
additional information
?
-
-
addition of uPA to natural killer cell receptor Ly49E positive adult and fetal natural killer cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively. Effects are dependent on receptor Ly49E
-
-
-
additional information
?
-
-
incubation of macrophages with uPA results in increased expression of paraoxonase 2. The resulting effects such as increase in macrophage oxidative stress, reactive oxygen formation, superoxide anion release, and cell-mediated low-density lipoprotein oxidation cannot be reproduced in macrophages harvested from p47phox-/- mice
-
-
-
additional information
?
-
-
incubation of THP-1 macrophage-like cells with uPA results in increased expression of paraoxonase 2. The effect requires uPA/uPA receptor interaction and is abolished by cell treatment with antioxidants. Presence of uPA increases macrophage oxidative stress, reactive oxygen formation, superoxide anion release, and cell-mediated low-density lipoprotein oxidation. Effects are related to uPA-mediated activation of NADPH oxidase
-
-
-
additional information
?
-
-
induction of endotoxin lipopolysaccharide-mediated uPA receptor expression is mediated through tyrosine phosphorylation of phophoglycerate kinase and heterogenous nuclear ribonucleoprotein C. This involves expression of uPA as an obligate intermediary
-
-
-
additional information
?
-
-
uterine natural killer cells may regulate extravillous trophoblast invasion and spiral artery remodeling via the uPA system
-
-
-
additional information
?
-
-
inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model, overview. The uPA/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors
-
-
-
additional information
?
-
-
uPA forms a complex with its cogante receptor uPAR, specific interctions, analysis, overview
-
-
-
additional information
?
-
-
uPA, uPA receptor, and plasminogen activator inhibitor form the urokinase-type plasminogen activator system
-
-
-
additional information
?
-
-
uPA-uPAR complexes concentrate the plasmin production that provides extracellular matrix proteolysis, weakened cell-cell contact, and increased cell motility. The proteolytic mechanisms include uPA-induced plasmin generation at focal adhesion sites, which results in extracellular matrix degradation and thus facilitates the detachment of the cell's trailing edge. Plasmin inhibitors can suppress cell migration both in vitro, mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury, overview. Urokinase signaling, overview
-
-
-
additional information
?
-
-
urokinase-type plasmin activator, uPA, binding to uPA receptor, uPAR, induces migration/invasion through multiple interactors including integrins, overview. ECRG2 binds specifically to the kringle domain of uPA, and forms a complex with uPA-uPAR, the trinary complex modifies the dynamical association of uPAR with beta1 integrins. Identification of ECRG2-binding sequence in uPA, overview. Complex disruption inhibits the Src/mitogen-activated protein kinase pathway, resulting in suppression of cell migration/invasion
-
-
-
additional information
?
-
-
uPA-induced phosphorylation of endothelial nitric oxide synthase, eNOS, which is inhibited by myristoylated PKI, a protein kinase A inhibitor
-
-
-
additional information
?
-
Mus musculus C57BL/6
-
urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice, depletion of macrophages leads to reduced hypertrophy of muscles, overview
-
-
-
additional information
?
-
Mus musculus C57BL/6
-
urokinase-type plasminogen activator plays essential roles in skeletal muscle regeneration and healing, macrophage depletion leads to impaired muscle regeneration, molecular mechanism, overview, the macrophage enzyme is essentially required for chemotaxis, mechanism independent of receptor binding, overview
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model, overview. The uPA/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[(N-benzylsulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
1-[3'-([3,5-difluoro-6-[5-methyl-2-(1H-tetrazol-1-yl)phenoxy]pyridin-2-yl]oxy)biphenyl-3-yl]methanamine
-
-
2-(1-hydroxynaphthalen-2-yl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2,6-dihydroxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-3-bromo-5-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-3-bromophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-3-fluorophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-3-methoxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-3-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-3-nitrophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-4-diethylaminophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-4-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-5-bromophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-5-chlorobiphenyl-3-yl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-5-fluorophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-5-methoxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-5-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxy-5-nitrophenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxybiphenyl-3-yl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
-
2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine
-
-
2-(4-chloro-7-(2-cyano-6-methoxyphenyl)isoquinolin-1-yl)guanidine
-
comparison of selectivity with t-plasminogen activator and plasmin
2-(4-chloro-7-(2-methoxyphenyl)isoquinolin-1-yl)guanidine
-
comparison of selectivity with t-plasminogen activator and plasmin
2-(4-chloro-7-(3-methoxyphenyl)isoquinolin-1-yl)guanidine
-
comparison of selectivity with t-plasminogen activator and plasmin
2-(7-(1,3-benzodioxol-5-yl)-4-chloroisoquinolin-1-yl)guanidine
-
comparison of selectivity with t-plasminogen activator and plasmin
2-(7-(1,3-benzodioxol-5-yl)isoquinolin-1-yl)guanidine
-
comparison of selectivity with t-plasminogen activator and plasmin
2-(7-phenylisoquinolin-1-yl)guanidine
-
comparison of selectivity with t-plasminogen activator and plasmin
2-([6-[(3'-carbamimidoylbiphenyl-3-yl)oxy]-3,5-difluoro-4-methylpyridin-2-yl]oxy)-4-(dimethylamino)benzoic acid
-
-
2-phenethyl-SO2-D-Ser-Ala-Arg-al
-
is an irreversible urokinase inhibitor, and an alkylating agent forming a covalent adduct with an active site of the enzyme
2-phenyl-1-H-benzoimidazole-5-carboxamidine
-
-
2-[(6-[[3',5-bis(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)-5-hydroxybiphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-3-methylbenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-(propan-2-yl)benzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methoxybenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-nitrobenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-5-methylbenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-6-methylbenzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]benzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-4-[3-(dimethylamino)pyrrolidin-1-yl]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
-
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-4-[[2-(dimethylamino)ethyl](methyl)amino]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
-
2-[(6-[[4'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
-
2-[(6-[[4-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[(6-[[5-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[(6-[[5-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-4-[3-(dimethylamino)pyrrolidin-1-yl]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[(6-[[6-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
-
2-[2-(7-amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
-
-
2-[2-(7-benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
-
-
2-[3-(7-amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)propyl]isothiourea hydrobromide
-
-
2-[3-(7-benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy]propyl)isothiourea hydrobromide
-
-
2-[[3,5-difluoro-6-([3'-[(methylamino)methyl]biphenyl-3-yl]oxy)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
-
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoro-4-(methylamino)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
-
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoro-4-(morpholin-4-yl)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
-
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoro-4-(piperazin-1-yl)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
-
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-4-(dimethylamino)-3,5-difluoropyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
-
3-(2-bromoethoxy)-7-nitro-1H-isochromen-1-one
-
-
3-(3-bromopropoxy)-4-trifluoroacetyl-1H-isochromen-1-one
-
-
3-(3-bromopropoxy)-7-nitro-1H-isochromen-1-one
-
-
3-(4-chloro-1-((diaminomethylene)amino)isoquinolin-7-yl)-5-methoxybenzoic acid
-
comparison of selectivity with t-plasminogen activator and plasmin
3-(4-chloro-1-((diaminomethylene)amino)isoquinolin-7-yl)benzoic acid
-
comparison of selectivity with t-plasminogen activator and plasmin
3-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]benzoic acid
-
-
3-[2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]phenyl]propanoic acid
-
-
4-(2-aminoethoxy)-N-(3-chloro-2-ethoxy-5-piperidin-1-ylphenyl)-3,5-dimethylbenzamide
-
inhibitor with moderate clearance level, high volume of distribution, and long half-life of 7.5 hours. More than 50 fold selective for uPA over all but one of the enzymes tested. Selectivity against trypsin is only 3- to 4fold
4-(4-chloro-1-((diaminomethylene)amino)isoquinolin-7-yl)benzoic acid
-
comparison of selectivity with t-plasminogen activator and plasmin
4-(dimethylamino)-2-[[6-([3'-[(dimethylamino)methyl]biphenyl-3-yl]oxy)-3,5-difluoropyridin-2-yl]oxy]benzoic acid
-
-
4-aminobenzamidine
-
competitive, no inhibition of the pro-uPA
4-chloro-3-alkoxyisocoumarin
-
competitive reversible inhibition
4-iodobenzo[b]thiophene-2-carboxamidine
-
APC-6860, competitive inhibition
4-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]benzoic acid
-
-
7-amino-3-(2-bromoethoxy)-1H-isochromen-1-one
-
-
alpha-1-antitrypsin
-
-
-
alpha-1-Proteinase inhibitor
-
-
-
alpha-2-Macroglobulin
-
-
-
alpha-Benzylsulfonyl-p-aminophenylalanine
-
-
Amiloride
-
significant reduction of hair follicle keratinocyte proliferation
Amiloride
-
competitive, no inhibition of the pro-uPA
Amiloride
-
a selective u-PA inhibitor
Anti-uPA IgG
-
-
-
antibody DS2
-
isolation and affinity maturation of a fully human recombinant antibody, that is specific to the human uPA and capable of inhibiting its enzymatic activity with an IC50 value in the low nanomolar range, overview. Ability of the DS2 antibody to preferentially localize at the tumor site compared with healthy organs
-
antibody IgG(DS2)
-
-
-
antibody scFv(DS2)
-
-
-
antipain
-
-
antithrombin
-
-
-
Aprotinin
-
-
benzamidine
-
-
benzamidine
-
-
benzo[b]thiophene-2-carboxamidine
-
APC-7377
concanavalin A
-
-
-
D-Phe-Phe-ArgCH2Cl
-
-
D-Ser-Ala-Arg-NH-(CH2)5-NH2
-
competitive inhibition
D-Ser-Ala-Arg-NH-(CH2)7-NH2
-
-
D-Ser-Ala-Arg-NH-(CH2)8-NH2
-
-
D-Ser-Ala-Arg-NH-(CH2)9-NH2
-
-
di-(4-acetamidophenyl) 1-[(N-benzyloxycarbonyl-D-seryl)-Lalanyl]amino-2-[4-(guanidino)phenyl]-ethanephosphonate trifluoroacetate
-
-
diphenyl (N-benzyloxycarbonyl-D-seryl-L-alanyl)amino-(3-guanylpropyl)methanephosphonate
-
50% inhibition at 0.000061 mM
diphenyl (N-benzyloxycarbonyl-D-seryl-L-alanyl)amino-(4-guanylbutyl)methanephosphonate
-
50% inhibition at 0.00025 mM
diphenyl (N-benzyloxycarbonyl-D-seryl-L-alanyl)amino-(4-guanylphenyl)methanephosphonate
-
50% inhibition at 0.0016 mM
diphenyl 1-(N-benzyloxycarbonyl-D-seryl-L-alanyl)amino-2-(4-guanylphenyl)ethanephosphonate
-
50% inhibition at 0.000057 mM
diphenyl 1-[(N-2-acetoadamantanyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-2-acetothiophenyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-benzenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-benzoyloxycarbonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-benzoylsulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-naphtalenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-o,o-dimethylbenzoyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-o-methylbenzoyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N-p-bromobenzenesulfonyl-D-seryl)-L-alanyl]-amino-2-(4-guanidinophenyl)ethane-phosphonate trifluoroacetate
-
-
diphenyl 1-[(N-p-cyanobenzenesulfonyl-D-seryl)-L-alanyl]-amino-2-(4-guanidinophenyl)ethane-phosphonate trifluoroacetate
-
-
diphenyl 1-[(N-p-methoxybenzenesulfonyl-D-seryl)-L-alanyl]-amino-2-(4-guanidinophenyl)ethane-phosphonate trifluoroacetate
-
-
diphenyl 1-[(N-p-methylbenzoyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
diphenyl 1-[(N2-thiophenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
-
ecotin
-
inhibits uPA almost 10000-fold less efficiently than trypsin, ecotin is expressed on the surface of filamentous bacteriophage, each of the selected ecotin variants (M84R, M84K, M84R/M85R and M84R/M85K) exhibits increased affinity for uPA when compared to wild-type ecotin, with ecotin M84R/M85R showing 2800-fold increase in binding affinity
-
ecotin
-
-
-
EDTA
-
inhibits binding of integrin alphanybeta3 to the enzyme
Endothelial cell/platelet type plasminogen activator inhibitor
-
-
-
enzyme-specific antibody
-
significant reduction of hair follicle keratinocyte proliferation
-
Fast-acting uPA inhibitor in plasma
-
-
-
Glu-Gly-Arg chloromethyl ketone
-
-
Glu-Gly-Arg-chloromethyl ketone
-
-
i-Boc-D-Ser-Ala-Arg-al
-
is an alkylating agent, and irreversibly inhibits urokinase by forming a covalent adduct with an active site of the enzyme
Leupeptin
-
-
Lima bean trypsin inhibitor
-
-
-
maspin
-
regulates uPA-dependent processes in vivo not involving its RCL sequence with Arg340, but is inable to directly inhibit uPA catalytic activity in vitro, binds the enzyme in both singlechain and double-chain forms, maspin is a member of the serpin family with a reactive center loop that is incompatible with proteinase inhibition by the serpin conformational change mechanism, overview
meloxicam
-
reduces enzyme secretion in chondral and synovial cultures downregulating the PA/plasmin system
methylprednisolone
-
reduces enzyme secretion in chondral and synovial cultures downregulating the PA/plasmin system
mexiletine
-
IC50 value above 1 mM, crystallographic data
mupain-1
-
i.e. CPAYSRYLDC, isolated from a murine peptide library and reconstructed, no inhibition of wild-type human enzyme, since the inhibitor is highly specific for the murine enzyme, but inhibition by the human enzyme mutant H99Y, overview, expression of mupain-1 peptide sequence in fusion with the N-terminal domains of the phage coat protein g3p in Escherichia coli
mupain-1
-
i.e. CPAYSRYLDC, isolated from a murine peptide library and reconstructed, competitive and highly selective inhibitor, R6 of mupain-1 is the P1 residue, extended binding interaction including the P5, P3, P2, P1, and P1' residues of mupain-1 and the specificity pocket, the catalytic triad, and the amino acids 41, 99 and 192 located in and around the active site of murine uPA, overview, expression of mupain-1 peptide sequence in fusion with the two N-terminal domains of g3p, D1 and D2 in Escherichia coli
myristoylated PKI
-
mPLI, a protein kinase A inhibitor, complete inhibition
-
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-prolinamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-[(4-aminobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-[(4-chlorobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-[(4-chlorobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-[(4-methylbenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-[(4-nitrobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
comparison of specificity with five additional trypsin-like serine-proteases
N-[3-(2-bromoethoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide
-
-
N-[3-(3-bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide
-
competitive reversible inhibition mechanism, the bromine occupies the same position as positively charged arginino mimetic groups, molecular modeling
N-[[4-(methoxycarbonyl)benzyl]sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
comparison of specificity with five additional trypsin-like serine-proteases
Naproxen
-
reduces enzyme secretion in chondral and synovial cultures downregulating the PA/plasmin system
PA inhibitor type 1
-
PAI-1, effects of uPA-PAI-1 are abrogated by the nitric-oxide synthase inhibitor N-D-nitro-L-arginine methyl ester. Dramatically elevated levels in case of acute lung injury
-
PAI-1
-
a proteolytic inhibitor of uPA, blocks the increase in proliferation of myoblasts induced by uPA
-
PAI-1
-
-
-
PAI-2
-
i.e. plasminogen activator inhibitor type 2, cell-surface enzyme:PAI-2 complex formation is reflective of complete enzyme inhibition, kinetic analysis of inhibition
-
PD 098059
-
hepatocyte growth factor-mediated uPA secretion by Hep-G2 cells is reduced with increasing concentrations of PD 098059
PD98059
-
the ERK MAP kinase inhibitor dramatically reduces the uPA expression in the frozen-thawed porcine uterus endometrial epithelium cells
penicilloic acid
-
-
Pentamidine
-
-
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
-
phenethylsulfonamidino-D-seryl-L-alanyl-L-argininal
-
-
phenylmethanesulfonyl fluoride
-
-
plasminogen activator inhibitor
-
PAI-1
-
plasminogen activator inhibitor 1
-
human
plasminogen activator inhibitor 1
-
phosphorylated uPA is less sensitive to inhibition than nonphosphorylated uPA
plasminogen activator inhibitor 1
-
binding of single-chain uPA moiety to the inhibitor occurs with lower affinity compared to binding of the two-chain uPA moiety
plasminogen activator inhibitor 1
-
phosphorylated enzyme is inhibited 50% at a concentration 4fold higher than nonphosphorylated enzyme
plasminogen activator inhibitor 1
-
i.e. PAI-1
plasminogen activator inhibitor 1
-
-
Plasminogen activator inhibitor 2
-
-
-
plasminogen activator inhibitor type-1
-
i.e. PAI type-1, the endogenous inhibitor expression is higher in myometrium than in myoma in the uterus myomatosus, overview
-
plasminogen activator inhibitor type-1
-
i.e. PAI-1, an endogenous inhibitor protein
-
plasminogen activator inhibitor-1
-
i.e. PAI-1, complexes the enzyme, binding structure, the 10-100-fold higher affinity of the uPA-PAI-1 complex compared with the free components depends on the bonus effect of bringing the binding areas on uPA and PAI-1 together on the same binding entity, overview, inhibitor mutants K71A/R78A/Y81A/K82A, K82A-R120A, and R78A-K124A show reduced binding to the enzyme and the enzyme receptors, effects of several mutations of the inhibitor protein on complex formation and endocytosis, overview
plasminogen activator inhibitor-1
-
-
plasminogen activator inhibitor-1
-
an endogenous inhibitor protein, i.e. PAI-1
plasminogen activator inhibitor-1
-
i.e. PAI-1, recombinantly expressed with an N-terminal His6-tag and purified from Escherichia coli cells, labeled with N,N0-dimethyl-N-(iodoacetyl)-N0-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine, i.e. P9-NBD-labeled PAI-1. Slow formation of a covalent serpin-protease complex between single-chain uPA and PAI-1 is significantly accelerated in the presence of specific dipeptide sequences
plasminogen activator inhibitor-1
-
i.e. PAI-1
plasminogen activator inhibitor-1
-
PAI-1
plasminogen activator inhibitor-1
-
PAI-1, specifically and rapidly inhibits urokinase-type plasminogen activator uPA and tissue-type plasminogen activator, tPA, EC 3.4.21.68. The PAI-1 reactive center loop serves as a bait to attract uPA onto the top of the PAI-1 molecule. P4P3' residues of the reactive center loop interact extensively with the uPA catalytic site, accounting for about two-thirds of the total contact area, also almost all uPA exosite loops, including the 37-, 60-, 97-, 147-, and 217-loops, are involved in the interaction with PAI-1, of the residues of the 37-loop, Arg-E37a plays the most important role, Michaelis complex formation, overview. The recombinant stable His-tagged PAI-1 mutant 14-1B containing four point mutations N150H, K154T, Q319L, and M354I, is expressed in Escherichia coli strain C41(DE3) using the expression vector pT7-PL
plasminogen activator inhibitor-2
-
i.e. PAI-2
-
plasminogen activator inhibitor-2
-
PAI-2
-
Plumbagin
-
leads to uPA inhibition and downregulation, inhibits adhesion, migration and invasion in HepG2 cells
Protease nexin I
-
-
-
Protein C inhibitor
-
-
-
Soybean trypsin inhibitor
-
-
-
staphylokinase
-
competitively inhibits plasminogen activation by endogenous uPA. The N-terminal residues of staphylokinase are important for inhibition
-
thieno[2,3-b]pyridine-2-carboxamidine
-
APC-7538
trans-3,4'-dimethyl-3-hydroxyflavanone
-
i.e. t-flavanone, a synthetic compound with hair growth enhancing activity that is effective against male pattern alopecia, inhibits the enzyme on the surface of keratinocytes, overview
trans-diphenyl N-(N-benzyloxycarbonyl-D-seryl-L-alanyl)amino-(4-(guanylmethyl)-cyclohexyl)methanephosphonate
-
50% inhibition at 0.0011 mM
tripeptidyl diphenyl phosphonates
-
irreversible inhibition
Trypsin
-
-
-
TX-1877
-
hypoxic cell radiosensitizer. Treatment of nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 with TX-1877, irradiation or TX-1877 with irradiation results in significant inhibition of matrix metalloproteinase-9 and uPA. Treatments also inhibit the para-aortic lymph node metastasis, however, do not prolong the survival in orthotopic model. In the subcutaneous model, tumors treated with TX-1877 and irradiation show significant reductions in volume
type-1 plasminogen activator inhibitors
-
primary endogenous inhibitors
-
upain-1
-
competitive, no inhibition of the pro-uPA
WXC-340
-
a selective u-PA inhibitor
-
[2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]phenyl]acetic acid
-
-
monoclonal antibody mU1
-
murine monoclonal antibody directed against murine uPA. mU1 blocks uPA-catalyzed plasminogen activation in vitro, as well as plasmin-mediated pro-uPA activation. Systemic administration of mU1 rescues mice treated with a uPA-activable anthrax protoxi and impairs uPA-mediated hepatic fibrinolysis in tissue-type plasminogen activator-deficient mice, resulting in a phenotype mimicking that of uPA/tPA double deficient mice
-
additional information
-
humanized murine ATF, i.e. an amino-terminal fragment of urokinase, represses 79% of membrane-associated enzyme activity on MDA-MB-231 cells, murine ATF represses 29% of activity
-
additional information
-
humanized murine ATF, i.e. an amino-terminal fragment of urokinase, represses 29% of membrane-associated enzyme activity on LLC cells, murine ATF represses 74% of activity
-
additional information
-
phage-displayed peptide library screening for murine uPA-binding peptide sequences, overview
-
additional information
-
development of potent uncharged inhibitors of uPA based upon the isocoumarin scaffold, bromine occupies the same position as positively charged arginino mimetic groups, structure activity relationships, inhibitor synthesis and molecular modeling, overview
-
additional information
-
the active form of uPA is bound to its high affinity receptor on the cell surface, where specific inhibitors modulate its enzymatic activity, such inhibitors also regulate the cell surface levels of uPA by triggering the internalization of the uPA-receptor-inhibitor complex via endocytosis
-
additional information
-
quantitative structure-activity relationship analysis of substituted 2-pyridinyl guanidines as selective inhibitors using QuaSAR descriptors of molecular modeling software MOE. uPA inhibitory activity of core-substitued 2-pyridinyl guanidines is influenced by their molecular shape, molecular flexibility and halogen atoms in the molecule. uPA inhibitory activity of 2-(5-chloropyridin-2-yl) guanidines with bulky substituents in position 3 is dependent on molecular lipophilicity, number of double bonds and spatial orientation of bulky substituents in the molecule
-
additional information
-
stable expression of dominant-negative MEK-1 in Hep-G2 cells decreases S hepatocyte growth factor-mediated uPA secretion
-
additional information
-
identification of potent, selective, and orally bioavailable non-amidine uPA inhibitors, binding in the S1 pocket, overview
-
additional information
-
Thrombin hydrolysis provides the mechanism of proteolytic inactivation of uPA cleavage of the Arg156-Phe157 enzyme bond that does not exclude nonproteolytic functioning of such peptide forms
-
additional information
-
the MAP kinase inhibitors SP600125, a JNK inhibitor, and SB203580, a p38 inhibitor, do not inhibit uPA in frozen-thawed porcine uterus endometrial epithelium cells
-
additional information
-
synthesis of peptides competing with uPA for binding to the specific uPA receptor, usage of the SAAC methodology to regioselectively label the peptides, overview
-
additional information
-
the autolysis loop in the catalytic domain of uPA is a potential inhibitory target. Three antibodies are potent inhibitors of uPA activity, two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and an active uPA-specific antibody by shielding the access of plasminogen to the active site, overview. 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. Antibody mAb-112 is a non-competitive inhibitor of S-2444 cleavage by uPA with a Ki similar to the Kd for mAb-112 binding to active two-chain uPA. The epitopes of the conformation-specific antibodies are all localized to the activation and/or autolysis loop, binding kinetic analysis and models of the three-dimensional structures, overview
-
additional information
-
efficacy of grape seed extract in negatively regulating uPA expression and cell migration using highly metastatic androgen-independent PC3 prostate cancer cells as a model. Grape seed extract inhibits and downregulates NFkB-dependent urokinase plasminogen activator promoter activity
-
additional information
-
no inhibition by LY294002 and AktI
-
additional information
-
synthesis and inhibitory potencies of d-Ser-Ala-Arg-NH-X peptides, overview. All compounds with a hydroxyl residue of an amide group do not inhibit urokinase, no inhibition by D-Ser-Ala-Arg-NH
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,3,8-trihydroxy-6-methylanthraquinone
-
i.e. emodin, an active compound of aloe. Emodin increases the fibrinolytic activity of fibroblast cells in a dose-dependent manner, linked to increased uPA activity and uPA gene up-regulation. Emodin also induces up-regulation of uPA inhibitor PAI-1. Up-regulations are independent of emodin's effect on nuclear factor kappaB. The effect on the uPA system may be via generation of reactive oxygen species
Ile-Ile
-
an Ile-Ile or Ile-Val dipeptide can induce limited enzyme activity in the single-chain zymogen form of uPA or its K158A variant, which cannot be activated proteolytically
Ile-Val
-
an Ile-Ile or Ile-Val dipeptide can induce limited enzyme activity in the single-chain zymogen form of uPA or its K158A variant, which cannot be activated proteolytically
integrin alpha v beta3
-
binds specifically to the enzyme and is required for plasminogen activation, overview
-
phorbol 12-myristate 13-acetate
-
stimulation of dental pulp cells by tumor necrosis factor-alpha results in increased uPA activity. Tumor necrosis factor-alpha-induced PA release is enhanced in the presence of phorbol 12-myristate 13-acetate
SB 203580
-
pretreatment of Hep-G2 cells with SB 203580 increases hepatocyte growth factor-mediated uPA secretion by 50-60%
tumor necrosis factor-alpha
-
stimulation of dental pulp cells results in increased uPA activity. Tumor necrosis factor-alpha-induced PA release is enhanced in the presence of phorbol 12-myristate 13-acetate
-
UK-356202
-
rapid, sensitive and selective method for detection in human plasma
interleukin beta
-
significantly induces uPA expression and activity via protein kinase Calpha-dependent JNK1/2 and NIK cascades. Induction is inhibited by pretreatment with the inhibitors of JNK1/2, SP600125, of protein kinase C, Ro31-8220 and Go6976, or of nuclear factor kappaB, helenalin, and by transfection with dominant negative mutants of protein kinase C alpha, NIK, and IKKbeta, and siRNAs of JNK1/2 and p65
-
additional information
-
pro-urokinase upregulates the expression of urokinase-type plasminogen activator in pulmonary arterial endothelial cells, but not the expression level of the uPA receptor
-
additional information
-
increased plasminogen activator activity in the lung by administering exogenous uPA or by using mice genetically deficient in the uPA inhibitor plasminogen activator inhibitor-1, PAI-1
-
additional information
-
binding of uPA to uPA receptor increases the catalytic efficiency by enhancing its activation by plasmin or other enzymes. uPAR promotes the invasive migration of hair follicles synergizing in manner dependent and independent of uPA during human prenatal morphogenesis
-
additional information
-
the enzyme is initially synthesized as single-chain proenzyme with an activity that is many orders of magnitude lower than those of the mature enzyme. Proteolytic cleavage of an exposed loop liberates a new amino terminus that inserts into a hydrophobic pocket and forms a stabilizing salt bridge with a ubiquitously conserved aspartate residue, resulting in a conformational change organizing the mature oxyanion hole
-
additional information
-
increase of uPA activity and expression by freezing/thawing process in porcine uterus endometrial epithelium cells
-
additional information
-
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
-
additional information
-
u-PAR in binding to u-PA initiates plasminogen activation. A cleavage-resistant u-PAR, cr-u-PAR, exhibits accelerated internalization and resurfacing due to direct association with the endocytic receptor alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein in the absence of the enzyme inhibitor complex of active u-PA and plasminogen activator inhibitor-1
-
additional information
-
uPA needs to be activated proteolytically. Sphingosine 1-phosphate receptor S1P1 overexpression in U-118 MG cells results in potent stimulation of uPA activity regardless of S1P treatment, expression of receptors S1P2 and S1P3 does not affect uPA activity
-
additional information
-
cytokeratin 8 ectoplasmic domain binding by a specific monoclonal antibody inhibits activation of plasminogen, the synthetic dodecapeptide corresponding to the epitope sequence, VKIALEVEIATY, binds uPA. The antibody increases adhesion of breast tumor cells to fibronectin
-
additional information
-
plasmin and urokinase-type plasminogen activator can activate each other through proteolytic cleavage
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.053
Benzyloxycarbonyl-Gly-Gly-Arg-amino-4-trifluoromethylcoumarin
-
-
0.052
GSGRSA
-
pH 7.5, 37C, protein substrate
0.6
GSGRSA
-
pH 7.5, 37C, peptide substrate
0.03
HYGRSA
-
pH 7.5, 37C, protein substrate
3.8
HYGRSA
-
pH 7.5, 37C, peptide substrate
0.053
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
wild-type, pH 8.0, 22C
0.079
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309S, pH 8.0, 22C
0.081
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309A, pH 8.0, 22C
0.087
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309AT, pH 8.0, 22C
0.102
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309V, pH 8.0, 22C
0.11
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309G, pH 8.0, 22C
0.129
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309N, pH 8.0, 22C
0.153
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309L, pH 8.0, 22C
0.175
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309D, pH 8.0, 22C
0.235
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309R, pH 8.0, 22C
0.268
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309H, pH 8.0, 22C
0.361
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309F, pH 8.0, 22C
0.452
L-pyroGlu-Gly-L-Arg-4-nitroanilide
-
mutant P309W, pH 8.0, 22C
0.08
L-pyroGlu-Gly-L-Arg-p-NA
-
pH 8.8, 37C
0.297
L-pyroglutamyl-glycyl-L-arginine 4-nitroanilide hydrochloride
-
pH 8.8, phosphorylated uPA
0.392
L-pyroglutamyl-glycyl-L-arginine 4-nitroanilide hydrochloride
-
pH 7.5, phosphorylated uPA
0.438
L-pyroglutamyl-glycyl-L-arginine 4-nitroanilide hydrochloride
-
pH 8.8, nonphosphorylated uPA
0.014
PFGRSA
-
pH 7.5, 37C, protein substrate
2.2
PFGRSA
-
pH 7.5, 37C, peptide substrate
0.000243
Plasminogen
-
pH 7.5, nonphosphorylated uPA
-
0.00092
Plasminogen
-
phosphorylated enzyme
-
0.001
Plasminogen
-
nonphosphorylated enzyme
-
0.017
Plasminogen
-
pH 7.5, phosphorylated uPA
-
0.1
pyroGlu-Gly-Arg-4-nitroanilide
-
pH 7.4, 37C, pro-uPA
0.13
pyroGlu-Gly-Arg-4-nitroanilide
-
pH 7.4, 37C, mature uPA
0.13
QRGRSA
-
pH 7.5, 37C, protein substrate
2.18
QRGRSA
-
pH 7.5, 37C, peptide substrate
0.051
S2444
-
pH 7.4, 25C, wild-type and mutant E301A, single-chain activator
0.052
S2444
-
pH 7.4, 25C, mutant K300H, single-chain activator
0.053
S2444
-
pH 7.4, 25C, mutant S303E, single-chain activator
0.054
S2444
-
pH 7.4, 25C, mutant K300A and K313A, single-chain activator
0.055
S2444
-
pH 7.4, 25C, mutant E301H, single-chain activator
0.058
S2444
-
pH 7.4, 25C, mutant Y306G, single-chain activator
0.059
S2444
-
pH 7.4, 25C, mutant K300W, single-chain activator
0.06
S2444
-
pH 7.4, 25C, mutant E301D, single-chain activator
0.074
S2444
-
pH 7.4, 25C, mutant K300W, two-chain activator
0.075
S2444
-
pH 7.4, 25C, mutant K300H, two-chain activator
0.077
S2444
-
pH 7.4, 25C, mutant K300A and S303E, two-chain activator
0.078
S2444
-
pH 7.4, 25C, wild-type, two-chain activator
0.08
S2444
-
pH 7.4, 25C, mutant K313A, two-chain activator
0.082
S2444
-
pH 7.4, 25C, mutant E301D, two-chain activator
0.085
S2444
-
pH 7.4, 25C, mutant Y306G, two-chain activator
0.087
S2444
-
pH 7.4, 25C, mutant E301A, two-chain activator
0.089
S2444
-
pH 7.4, 25C, mutant E301H, two-chain activator
0.13
YGAKAY
-
pH 7.5, 37C, protein substrate
2.3
YGAKAY
-
pH 7.5, 37C, peptide substrate
0.608
L-pyroglutamyl-glycyl-L-arginine 4-nitroanilide hydrochloride
-
pH 7.5, nonphosphorylated uPA
additional information
additional information
-
-
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
binding kinetics of enzyme with enzyme receptors VLDLR-I, SorLA, or LRP-1A , overview
-
additional information
additional information
-
kinetic effects of dipeptides on the catalytic activity of single-chain uPA and two-chain uPA toward the chromogenic substrate S-2444, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0075
L-pyroglutamyl-glycyl-L-arginine 4-nitroanilide hydrochloride
-
pH 8.8, nonphosphorylated uPA
0.0113
L-pyroglutamyl-glycyl-L-arginine 4-nitroanilide hydrochloride
-
pH 7.5, nonphosphorylated uPA
0.0383
Plasminogen
-
pH 7.5, nonphosphorylated uPA
-
12.4
Plasminogen
-
nonphosphorylated enzyme
-
14.1
Plasminogen
-
phosphorylated enzyme
-
0.73
pyroGlu-Gly-Arg-4-nitroanilide
-
pH 7.4, 37C, pro-uPA
773
pyroGlu-Gly-Arg-4-nitroanilide
-
pH 7.4, 37C, mature uPA
0.0077
S2444
-
pH 7.4, 25C, mutant K300A, single-chain activator
0.0085
S2444
-
pH 7.4, 25C, mutant K300W, single-chain activator
0.027
S2444
-
pH 7.4, 25C, mutant E301A, single-chain activator
0.029
S2444
-
pH 7.4, 25C, mutant Y306G, single-chain activator
0.047
S2444
-
pH 7.4, 25C, mutant E301D, single-chain activator
0.065
S2444
-
pH 7.4, 25C, mutant K300H, single-chain activator
0.32
S2444
-
pH 7.4, 25C, mutant S303E, single-chain activator; pH 7.4, 25C, wild-type, single-chain activator
0.33
S2444
-
pH 7.4, 25C, mutant K313A, single-chain activator
1.5
S2444
-
pH 7.4, 25C, mutant E301H, single-chain activator
22
S2444
-
pH 7.4, 25C, mutant Y306G, two-chain activator
27
S2444
-
pH 7.4, 25C, mutant K300W, two-chain activator
60
S2444
-
pH 7.4, 25C, mutant K300A, two-chain activator
83
S2444
-
pH 7.4, 25C, mutant E301H, two-chain activator
180
S2444
-
pH 7.4, 25C, wild-type and mutant S303E, two-chain activator
190
S2444
-
pH 7.4, 25C, mutant K313A, two-chain activator
200
S2444
-
pH 7.4, 25C, mutant E301A, two-chain activator
270
S2444
-
pH 7.4, 25C, mutant E301D, two-chain activator
350
S2444
-
pH 7.4, 25C, mutant K300H, two-chain activator
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.12
pyroGlu-Gly-Arg-4-nitroanilide
-
pH 7.4, 37C, pro-uPA
19261
99
pyroGlu-Gly-Arg-4-nitroanilide
-
pH 7.4, 37C, mature uPA
19261
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0039
2-(1-hydroxynaphthalen-2-yl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0019
2-(2,6-dihydroxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.00028
2-(2-hydroxy-3-bromo-5-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.00025
2-(2-hydroxy-3-bromophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.00055
2-(2-hydroxy-3-fluorophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0036
2-(2-hydroxy-3-methoxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.008
2-(2-hydroxy-3-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0009
2-(2-hydroxy-3-nitrophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.013
2-(2-hydroxy-4-diethylaminophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0036
2-(2-hydroxy-4-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0037
2-(2-hydroxy-5-bromophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0005
2-(2-hydroxy-5-chlorobiphenyl-3-yl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0028
2-(2-hydroxy-5-fluorophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0036
2-(2-hydroxy-5-methoxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0075
2-(2-hydroxy-5-methylphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0033
2-(2-hydroxy-5-nitrophenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0004
2-(2-hydroxybiphenyl-3-yl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.0055
2-(2-hydroxyphenyl)-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.00018
2-(4-chloro-7-(2-cyano-6-methoxyphenyl)isoquinolin-1-yl)guanidine
-
-
0.0001
2-(4-chloro-7-(2-methoxyphenyl)isoquinolin-1-yl)guanidine
-
-
0.000083
2-(4-chloro-7-(3-methoxyphenyl)isoquinolin-1-yl)guanidine
-
-
0.0001
2-(7-(1,3-benzodioxol-5-yl)-4-chloroisoquinolin-1-yl)guanidine
-
-
0.00034
2-(7-(1,3-benzodioxol-5-yl)isoquinolin-1-yl)guanidine
-
-
0.0004
2-(7-phenylisoquinolin-1-yl)guanidine
-
-
0.055
2-phenyl-1-H-benzoimidazole-5-carboxamidine
-
pH 7.4, 37C
0.00002
2-[2-(7-amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
-
pH 8.8, 25C
0.000084
2-[2-(7-benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
-
pH 8.8, 25C
0.000038
2-[3-(7-amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)propyl]isothiourea hydrobromide
-
pH 8.8, 25C
0.00001
2-[3-(7-benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy]propyl)isothiourea hydrobromide
-
pH 8.8, 25C
0.0042
3-(2-bromoethoxy)-7-nitro-1H-isochromen-1-one
-
pH 8.8, 25C
0.014
3-(3-bromopropoxy)-4-trifluoroacetyl-1H-isochromen-1-one
-
pH 8.8, 25C
0.0043
3-(3-bromopropoxy)-7-nitro-1H-isochromen-1-one
-
pH 8.8, 25C
0.000009
3-(4-chloro-1-((diaminomethylene)amino)isoquinolin-7-yl)-5-methoxybenzoic acid
-
-
0.000037
3-(4-chloro-1-((diaminomethylene)amino)isoquinolin-7-yl)benzoic acid
-
-
0.000082
4-(4-chloro-1-((diaminomethylene)amino)isoquinolin-7-yl)benzoic acid
-
-
0.0395
4-aminobenzamidine
-
pH 7.4, 37C, mature uPA
0.00021
4-iodobenzo[b]thiophene-2-carboxamidine
-
pH 7.4, 37C
0.065
7-amino-3-(2-bromoethoxy)-1H-isochromen-1-one
-
pH 8.8, 25C
0.005
Amiloride
-
pH 7.4, 37C, mature uPA
0.097
benzamidine
-
pH 7.4, 37C
0.0023
benzo[b]thiophene-2-carboxamidine
-
pH 7.4, 37C
0.0004
mupain-1
-
pH 7.4, 37C
0.0036
mupain-1
-
pH 7.4, 37C, mutant V41K/H99Y/Q192K
0.0069
mupain-1
-
pH 7.4, 37C, mutant V41K/H99Y
0.0153
mupain-1
-
pH 7.4, 37C, mutant H99Y
0.0077
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
-
0.013
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-prolinamide
-
-
0.02
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide
-
-
0.036
N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
-
0.018
N-[(4-aminobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
-
0.0076
N-[(4-chlorobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
-
0.023
N-[(4-chlorobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide
-
-
0.01
N-[(4-methylbenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
-
0.024
N-[(4-nitrobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
-
0.0014
N-[3-(2-bromoethoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide
-
pH 8.8, 25C
0.000034
N-[3-(3-bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide
-
pH 8.8, 25C
0.018
N-[[4-(methoxycarbonyl)benzyl]sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide
-
-
0.000002
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
pH 7.4, 37C, compound uPA-I5
0.000003
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
pH 7.4, 37C, compound uPA-I6
0.000006
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
pH 7.4, 37C, compound uPA-I3
0.000014
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
pH 7.4, 37C, compound uPA-I4
0.000021
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
pH 7.4, 37C, compound uPA-I1
0.000028
phenethylsulfonamidino-D-seryl-L-alanyl(P2)-L-argininal
-
pH 7.4, 37C, compound uPA-I2
0.063
thieno[2,3-b]pyridine-2-carboxamidine
-
pH 7.4, 37C
0.0022
upain-1
-
pH 7.4, 37C, mature uPA
0.0063
D-Ser-Ala-Arg-NH-(CH2)5-NH2
-
pH 8.8, 37C
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
-
kinetic effects of dipeptides on the inhibition of single-chain uPA and two-chain uPA, overview. Stopped-flow kinetics of P9-NBD-labeled PAI-1, 25C, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000035
1-[(N-benzylsulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.013
1-[3'-([3,5-difluoro-6-[5-methyl-2-(1H-tetrazol-1-yl)phenoxy]pyridin-2-yl]oxy)biphenyl-3-yl]methanamine
-
pH not specified in the publication, temperature not specified in the publication
0.000098
2-([6-[(3'-carbamimidoylbiphenyl-3-yl)oxy]-3,5-difluoro-4-methylpyridin-2-yl]oxy)-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0027
2-[(6-[[3',5-bis(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000023
2-[(6-[[3'-(aminomethyl)-5-hydroxybiphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00054
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-3-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00068
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-(propan-2-yl)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00022
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methoxybenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00024
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0013
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-nitrobenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0035
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-5-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.026
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-6-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00084
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000025
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-4-[3-(dimethylamino)pyrrolidin-1-yl]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0001
2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-4-[[2-(dimethylamino)ethyl](methyl)amino]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.03
2-[(6-[[4'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000089
2-[(6-[[4-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000039
2-[(6-[[5-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000015
2-[(6-[[5-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-4-[3-(dimethylamino)pyrrolidin-1-yl]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.03
2-[(6-[[6-amino-3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]-4-methylbenzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.03
2-[[3,5-difluoro-6-([3'-[(methylamino)methyl]biphenyl-3-yl]oxy)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00013
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoro-4-(methylamino)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0009
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoro-4-(morpholin-4-yl)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000065
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoro-4-(piperazin-1-yl)pyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00053
2-[[6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-4-(dimethylamino)-3,5-difluoropyridin-2-yl]oxy]-4-(dimethylamino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.02
3-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.03
3-[2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]phenyl]propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000072
4-(2-aminoethoxy)-N-(3-chloro-2-ethoxy-5-piperidin-1-ylphenyl)-3,5-dimethylbenzamide
-
-
0.03
4-(dimethylamino)-2-[[6-([3'-[(dimethylamino)methyl]biphenyl-3-yl]oxy)-3,5-difluoropyridin-2-yl]oxy]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.03
4-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0000089
antibody IgG(DS2)
-
pH 7.4, 22C
-
0.0000067
antibody scFv(DS2)
-
pH 7.4, 22C
-
0.0000067
di-(4-acetamidophenyl) 1-[(N-benzyloxycarbonyl-D-seryl)-Lalanyl]amino-2-[4-(guanidino)phenyl]-ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.000008
diphenyl 1-[(N-2-acetoadamantanyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000069
diphenyl 1-[(N-2-acetothiophenyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000026
diphenyl 1-[(N-benzenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000043
diphenyl 1-[(N-benzoyloxycarbonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.000005
diphenyl 1-[(N-benzoylsulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000058
diphenyl 1-[(N-naphthalenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.000006
diphenyl 1-[(N-o,o-dimethylbenzoyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000044
diphenyl 1-[(N-o-methylbenzoyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000066
diphenyl 1-[(N-p-bromobenzenesulfonyl-D-seryl)-L-alanyl]-amino-2-(4-guanidinophenyl)ethane-phosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000062
diphenyl 1-[(N-p-cyanobenzenesulfonyl-D-seryl)-L-alanyl]-amino-2-(4-guanidinophenyl)ethane-phosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000058
diphenyl 1-[(N-p-methoxybenzenesulfonyl-D-seryl)-L-alanyl]-amino-2-(4-guanidinophenyl)ethane-phosphonate trifluoroacetate
-
pH 8.8, 37C
0.000007
diphenyl 1-[(N-p-methylbenzoyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0000015
diphenyl 1-[(N2-thiophenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
-
pH 8.8, 37C
0.0081
[2-[(6-[[3'-(aminomethyl)biphenyl-3-yl]oxy]-3,5-difluoropyridin-2-yl)oxy]phenyl]acetic acid
-
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
-
additional information
-
enzyme activity in different tissues with and without inhibitor treatment, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
-
assay at
7.5 - 9.5
-
phosphorylated uPA
7.5
-
assay at
7.6
-
assay at
8
-
assay at
8.3
-
assay at
8.5 - 9
-
-
8.8 - 9.5
-
nonphosphorylated uPA
8.8
-
assay at
8.8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at room temperature
25
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
silencing of transmembrane protein Notch1 by siRNA results in significant reduction in the expression of uPA and matrix metalloproteinase-9 gene transcripts. Knock-down of Notch also reduces the mRNA expression and protein levels of uPA and matrix metalloproteinase-9
Manually annotated by BRENDA team
-
melanoma cell
Manually annotated by BRENDA team
-
A431 epidermoid carcinoma cells
Manually annotated by BRENDA team
-
A-549 alveolar epithelial cell cultured on a fibrin matrix, stimulation by interleukin 1beta results in increased levels of enzyme in culture supernatant
Manually annotated by BRENDA team
-
patients with common variable immunodeficiency show increased levels of plasma uPA
Manually annotated by BRENDA team
-
uPA shows extensive colocalization with alpha-granule proteins in both cultured Quebec platelet disease megakaryocytes and platelets, and with plasminogen in Quebec platelet disease platelets
Manually annotated by BRENDA team
-
brain tissue of thermally injured rats displays an increase in the brain water content and the presence of Evans blue, temporally associated with an increased expression of endogenous tPA and uPA. Peripheral thermal injury does induce an increase in the permeability of the blood brain barrier
Manually annotated by BRENDA team
-
induction of lateral fluid percussion brain injury results in up-regulation of uPA and ERK mitogen-activated protein kinase. uPA contributes to the impairment of sodium nitroprusside and PGE2-mediated cerebrovasodilatation through activation of low-density lipoprotein receptor and ERK mitogen-activated protein kinase
Manually annotated by BRENDA team
-
from ME7-infected mice
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
from ME7-infected mice
-
Manually annotated by BRENDA team
-
a murine microglial cell line
Manually annotated by BRENDA team
-
standard model of the balloon catheter injury of the carotid. Periadventitial application of recombinant uPA significantly reduces lumen size and vessel area encompassed by the external lamina both 1 and 4 days after treatment.In fallatory cells accumulate in the arterial adventitia at both 1 and 4 days after uPA treatment. Four days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation-related genes are differentially expressed
Manually annotated by BRENDA team
-
very low enzyme content
Manually annotated by BRENDA team
-
differences in uPA and uPAR expression and clinicopathologic features of patients with mismatch repair-proficient colorectal cancer, immunohistochemic tissue analysis, overview
Manually annotated by BRENDA team
-
recombinant two-chain and single-chain enzyme
Manually annotated by BRENDA team
-
single chain, activated urokinase
Manually annotated by BRENDA team
-
pro-uPA and mature uPA
Manually annotated by BRENDA team
-
recombinant pro-uPA, expressed in Escherichia coli
Manually annotated by BRENDA team
-
silencing of transmembrane protein Notch1 by siRNA results in significant reduction in the expression of uPA and matrix metalloproteinase-9 gene transcripts. Knock-down of Notch also reduces the mRNA expression and protein levels of uPA and matrix metalloproteinase-9
Manually annotated by BRENDA team
-
established by a spontaneous transformation of endothelial cells of a human umbilical vein, with a novel substitution in the kringle structure
Manually annotated by BRENDA team
-
pulmonary arterial
Manually annotated by BRENDA team
-
outer root sheath keratinocyte of vibrissa follicle
Manually annotated by BRENDA team
-
A-549 alveolar epithelial cell cultured on a fibrin matrix, stimulation by interleukin 1beta results in increased levels of enzyme in culture supernatant
Manually annotated by BRENDA team
-
gastric biopsy probes. uPA, uPA receptor and inhibitor PAI-1 are expressed in H+/K+ ATPase- and vesicular monoamine transporter 2-expressing cells. uPA is also expressed in pepsinogen- and uPA receptor-containing cells. In each case, expression is increased in response to Helicobacter pylori, and for uPA, but not the receptor or PAI-1, requires the virulence factor CagE. Helicobacter pylori also stimulates soluble and cell surface-bound uPA activity
Manually annotated by BRENDA team
-
outermost epithelial cells of the hair follicle
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
uPA, seprase and pipeptidylaminopeptidase IV immunoreactivity is found in dysplastic and cancer cells as well as in stromal cells adjacent to dysplasia and cancer sites, but not in normal epithelium. There is a significant association between uPA expression and sex, tumor size and histological classification in carcinomas. Squamous cell carcinoma lines display higher levels of uPA, seprase and dipeptidylaminopeptidase IV than normal esophageal epithelial cell lines
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
outer root sheath keratinocyte of vibrissa follicle
Manually annotated by BRENDA team
-
uPAR is overexpressed in outer root sheath and interfollicle epidermis, and expressed in the outermost epithelial cells of the hair follicle and the basal keratinocytes of epidermis, the expression decreases with the development of the hair follicle
Manually annotated by BRENDA team
-
human recombinant uPA induces stem cell migration. Retrovirus-mediated overexpression of uPA and uPA receptor in neuroblastoma NB-1691 cells induced robust migration of stem cells toward NB-1691 cell-conditioned media, compared with media derived from wild-type NB-1691 cells. Depletion of uPA from PC-3 prostate cancer cell-conditioned medium blocks stem cell migration
Manually annotated by BRENDA team
-
implanted subcutaneously or orthotopically to nude mice
Manually annotated by BRENDA team
-
hearts with end-stage failure and fibrosis have macrophage accumulation and elevated plasminogen activator activity, mechanisms that link macrophage accumulation and plasminogen activator activity with cardiac fibrosis, overview
Manually annotated by BRENDA team
-
treatment with H2O2 upregulates expression of uPA. Hepatocyte growth factor modulates Rac-1 regulated production of reactive oxygen species through activation of Akt and reactive oxygen species regulates uPA production via MAP kinase
Manually annotated by BRENDA team
-
treatment with H2O2 upregulates expression of uPA. Hepatocyte growth factor modulates Rac-1 regulated production of reactive oxygen species through activation of Akt and reactive oxygen species regulates uPA production via MAP kinase
Manually annotated by BRENDA team
-
a hepatic stellate cell line
Manually annotated by BRENDA team
-
fibrosarcoma cell line
Manually annotated by BRENDA team
-
fibrosarcoma cell
Manually annotated by BRENDA team
-
a fibrosarcoma cell line
Manually annotated by BRENDA team
-
colon adenocarcinoma cell
Manually annotated by BRENDA team
-
implanted subcutaneously or orthotopically to nude mice
Manually annotated by BRENDA team
-
outer root sheath keratinocyte of vibrissa follicle
Manually annotated by BRENDA team
-
basal keratinocytes of epidermis at the hair follicle. Expression of uPA and uPA receptor is selectively induced at the very tip of the leading edge of the keratinocytes
Manually annotated by BRENDA team
-
tubule cells
Manually annotated by BRENDA team
-
in mice model for kidney ischemia reperfusion injury, deficiency for uPA receptor, but not uPA protects from ischemia reperfusion injury. In the allogenic kidney transplant model, uPA receptor but not uPA deficiency of the allograft causes superior recipient survival and strongly attenuates loss of renal function
Manually annotated by BRENDA team
-
silencing of transmembrane protein Notch1 by siRNA results in significant reduction in the expression of uPA and matrix metalloproteinase-9 gene transcripts. Knock-down of Notch also reduces the mRNA expression and protein levels of uPA and matrix metalloproteinase-9
Manually annotated by BRENDA team
-
asthma model mice
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
asthma model mice
-
Manually annotated by BRENDA team
-
human lung cancer cell line H1415, activation of uPA and uPA receptor in malignant solid tumors augments neural and mesenchymal stem cell tropism. Expression levels of uPA receptor on human solid tumor cell linescorrelates with levels of uPA and soluble uPA receptor in tumor cell-conditioned media
Manually annotated by BRENDA team
-
lung fibroblast cell line
Manually annotated by BRENDA team
-
from bone-marrow
Manually annotated by BRENDA team
-
blood monocyte-derived
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
breast cancer cell
Manually annotated by BRENDA team
-
adriamycine-resistant subline of MCF-7
Manually annotated by BRENDA team
-
a breast cancer cell line
Manually annotated by BRENDA team
-
subline of MDA-MB-231, stably transfected with the bacterial lacZ gene
Manually annotated by BRENDA team
-
CD34+ progenitor cells express normal amounts of uPA, while their differentiation into megakaryocytes results in abnormally increased expression of the uPA gene but not the flanking genes for vinculin or calcium/calmodulin-dependent protein kinase IIgamma on chromosome 10. uPA shows extensive colocalization with alpha-granule proteins in both cultured Quebec platelet disease megakaryocytes and platelets, and with plasminogen in Quebec platelet disease platelets
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
uPA localizes strongly to natural killer cells of the placental bed, especially at 8-10 weeks of gestation. uPA activity is similar in uterine natural killer cell culture supernatant compared with total unseparated decidual cells. uPA receptor in uterine natural killer cell lysates is significantly stronger than in total decidual cell lysates. Inhibitors PAI-1 and PAI-2 are not detected in uterine natural killer cell culture supernatants
Manually annotated by BRENDA team
-
retrovirus-mediated overexpression of uPA and uPA receptor in neuroblastoma NB-1691 cells induced robust migration of stem cells toward NB-1691 cell-conditioned media, compared with media derived from wild-type NB-1691 cells
Manually annotated by BRENDA team
-
activation of uPA and uPA receptor in malignant solid tumors augments neural and mesenchymal stem cell tropism. Expression levels of uPA receptor on human solid tumor cell lines correlates with levels of uPA and soluble uPA receptor in tumor cell-conditioned media
Manually annotated by BRENDA team
-
activation of uPA and uPA receptor in malignant solid tumors augments neural and mesenchymal stem cell tropism. Expression levels of uPA receptor on human solid tumor cell lines correlates with levels of uPA and soluble uPA receptor in tumor cell-conditioned media
Manually annotated by BRENDA team
-
study on cocaine-induced conditioned-place preference in rats with bilateral intra-accumbens injections of uPA-expressing lentiviral vectors. Overexpression of uPA in the nucleus accumbens significantly augments cocaine-induced place preference. Reinstatement with a low dose of cocaine produces significantly greater preference to the cocaine-associated context. Inhibition of tuPA expression using doxycycline abolishes the augmented acquisition produced by overexpression of uPA but not the expression of the cocaine-induced conditioned-place preference. Cocaine-induced cocaine-induced conditioned-place preference and reinstatement may be dependent on active extracellular uPA
Manually annotated by BRENDA team
-
activation of uPA and uPA receptor in malignant solid tumors augments neural and mesenchymal stem cell tropism. Expression levels of uPA receptor on human solid tumor cell lines correlates with levels of uPA and soluble uPA receptor in tumor cell-conditioned media. Depletion of uPA from PC-3 prostate cancer cell-conditioned medium blocks stem cell migration
Manually annotated by BRENDA team
-
in a severe combined immunodeficient-human mouse model, PC-3 cells are the major source of uPA in the experimental bone tumor. Injection of uPA-silenced PC-3 cells in bone xenografts results in significant reduction of bone tumor burdens and protection of trabecular bones from destruction. The suppressed tumor growth is associated with the level of uPA expression but not with its activity. An increase in the expression of PAI-1, the endogenous uPA inhibitor, is found during in vitro tumor-stromal interactions. Up-regulation of PAI-1 in bone stromal cells and preosteoclasts/osteoblasts is due to soluble factor(s) released by PC cells, and the enhanced PAI-1 expression in turn stimulated PC cell migration
Manually annotated by BRENDA team
-
silencing of transmembrane protein Notch1 by siRNA results in significant reduction in the expression of uPA and matrix metalloproteinase-9 gene transcripts. Knock-down of Notch also reduces the mRNA expression and protein levels of uPA and matrix metalloproteinase-9
Manually annotated by BRENDA team
-
granulocytes, monocytes
Manually annotated by BRENDA team
-
uPA localizes strongly to natural killer cells of the placental bed, especially at 8-10 weeks of gestation. uPA activity is similar in uterine natural killer cell culture supernatant compared with total unseparated decidual cells. uPA receptor in uterine natural killer cell lysates is significantly stronger than in total decidual cell lysates. Inhibitors PAI-1 and PAI-2 are not detected in uterine natural killer cell culture supernatants
Manually annotated by BRENDA team
-
expression levels of urokinase-type plasminogen activator system in radical prostatectomy specimens, overview
Manually annotated by BRENDA team
-
overexpression of uPA mRNA in various stages of surgically excised pterygia specimens and cultured pterygium fibroblasts, expression is increased significantly following the progression of the pterygium, quantitative real-time PCR analysis, overview
Manually annotated by BRENDA team
-
activation of uPA and uPA receptor in malignant solid tumors augments neural and mesenchymal stem cell tropism. Expression levels of uPA receptor on human solid tumor cell lines correlates with levels of uPA and soluble uPA receptor in tumor cell-conditioned media
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
basal keratinocytes of epidermis
Manually annotated by BRENDA team
-
in sputum derived from patients with house dust mite allergic asthma, the medium concentration of uPA is significantly greater than in healthy control patients. The sputum concentration of uPA correlates with sputum total cell count and with logarithmically transformed exhaled nitric oxide concentration, but not with FEV1 or bronchial reactivity to histamine. Tge effect of uPA seems to be independent of its fibrinolytic activity
Manually annotated by BRENDA team
-
breast cancer cell
Manually annotated by BRENDA team
-
fibroblast cell
Manually annotated by BRENDA team
-
activation of uPA and uPA receptor in malignant solid tumors augments neural and mesenchymal stem cell tropism. Expression levels of uPA receptor on human solid tumor cell lines correlates with levels of uPA and soluble uPA receptor in tumor cell-conditioned media
Manually annotated by BRENDA team
-
lymphoma cells
Manually annotated by BRENDA team
-
a histiocytic lymphoma cell line
Manually annotated by BRENDA team
-
lung fibroblast cell line
Manually annotated by BRENDA team
additional information
-
uPA is expressed differentially in colon and rectal cancers, expression analysis, overview
Manually annotated by BRENDA team
additional information
-
increased uPA expression in several epileptogenic pathologies, including hippocampal sclerosis, and in developmental glioneuronal lesions, such as focal cortical dysplasia, cortical tubers in patients with the tuberous sclerosis complex and in gangliogliomas, immunohistochemic analysis, overview
Manually annotated by BRENDA team
additional information
-
no or poor expression of uPA in LS513 normal fibroblast
Manually annotated by BRENDA team
additional information
-
quantitative and immunuhistochemic analysis of the urokinase plasminogen activator, its cognate receptor uPAR and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas, overview
Manually annotated by BRENDA team
additional information
-
strong expression of uPA in addition to a Gleason score, positive surgical margin, and lymph node metastasis
Manually annotated by BRENDA team
additional information
-
the uPA receptor, a GPI-linked cell surface protein, occurs in macrophages infiltrating the central nervous system, and in the cerebrospinal fluid during a number of CNS pathologies
Manually annotated by BRENDA team
additional information
-
uPA and uPA receptor are expressed during invasive migration of the hair follicle, not under normal circumstances. uPAR promotes the invasive migration of hair follicles synergizing in manner dependent and independent of uPA during human prenatal morphogenesis
Manually annotated by BRENDA team
additional information
-
uPA expression analysis in lung, overview
Manually annotated by BRENDA team
additional information
-
urokinase is overexpressed in several tumors
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6
-
the uPA receptor, a GPI-linked cell surface protein, occurs in macrophages infiltrating the central nervous system, and in the cerebrospinal fluid during a number of CNS pathologies
-
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6J
-
uPA expression analysis in lung, overview
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
on keratinocytes
Manually annotated by BRENDA team
-
the active form of uPA is bound to its high affinity receptor uPAR on the cell surface
Manually annotated by BRENDA team
-
extracellular matrix, the active form of uPA is bound to its high affinity receptor uPAR on the cell surface
-
Manually annotated by BRENDA team
-
the enzyme is secreted by cell culture of the breast cancer cell line MDA-MB-231
-
Manually annotated by BRENDA team
-
the enzyme is secreted by cell cultures to the supernatant
-
Manually annotated by BRENDA team
-
uPA is secreted by cells as a single-chain polypeptide
-
Manually annotated by BRENDA team
-
uPA is secreted from glioblastoma cells as inactive pro-uPA and is converted to an active form at the cell surface where it binds to its receptor uPAR
-
Manually annotated by BRENDA team
-
uPA secretion from human lung fibroblasts
-
Manually annotated by BRENDA team
-
secreted in inactive form
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
-
Manually annotated by BRENDA team
additional information
-
cytokeratin 8 ectoplasmic domain colocalizes with uPA and actin, and binds plasminogen in MCF-10A neoT cells, overview
-
Manually annotated by BRENDA team
additional information
-
the uPA receptor is concentrated in caveolae, special intrusions of the plasma membrane maintained by the membrane protein caveolin. Urokinase stabilizes the vitronectin-binding conformation of the uPAR and thus stimulates a vitronectin-dependent adhesion of some cells
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
-
rat, HPLC gel filtration
29677
50000
-
recombinant uPA, native PAGE
707064
52000
-
human, high-molecular weight two-chain form
29663
55000
-
-
652910
additional information
-
nucleotide and deduced amino acid sequence
29661
additional information
-
amino-terminal fragment; systematic mutational analysis of the receptor-binding region
29662
additional information
-
plasmin, plasma kallikrein, trypsin, thermolysin and cathepsin B and L cleave pro-uPA at the peptide bond Lys158-Ile159 which converts pro-uPA into the enzymatically active high-molecular weight two-chain form
29663
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 52000, SDS-PAGE
?
-
x * 55000, SDS-PAGE
?
-
x * 45000, SDS-PAGE, rat
?
-
x * 15800 + x * 14200 + x * 8850 + x * 8550, rat, SDS-PAGE under reducing conditions, x * 24500 + x * 23000, rat, SDS-PAGE under nonreducing conditions
?
-
x * 52000
?
-
x * 54000
?
-
x * 53000, pro-uPA, SDS-PAGE
?
-
x * 54000, single-chain proenzyme, SDS-PAGE
monomer
-
1 * 50000, recombinant uPA, SDS-PAGE
additional information
-
the two-polypeptide of the high-molecular-weight two-chain form are linked by disulfide bonds, A-chain MW 20000 and B-chain MW 32000
additional information
-
exists in single and two-chain forms, domain structure and interactions of recombinant urokinase-type plasminogen activator, the enzyme is composed of an epidermal growth factor-like, a kringle and a serine protease module
additional information
-
the amino-terminal fragment ATF of uPA contains an EGF-like and a kringle domain, involved in the binding of the receptor, chain B contains the catalytic site and maintains the ability to activate plasminogen also when it is not bound to the receptor, the C-terminus of the N-terminal region contains a sequence that interacts with alphaVbeta3 integrin and is relevant for cell migration
additional information
-
structure of uPA and uPAR complex in water and specific interactions between uPA and uPAR, analysis by classical molecular mechanics simulations and ab initio molecular orbital calculations based on fragment molecular orbital method, overview. 20-26 amino acid residues of uPA are important for the binding between uPA and uPAR, and electrostatic interactions largely contribute to the binding, overview
additional information
-
the urokinase molecule consists of 3 structural domains: the N-terminal domain homologous to the epidermal growth factor-like domain, the kringle domain, and the C-terminal proteolytic domain, domain structure of proform and mature form of uPA, overview
additional information
-
models of the three-dimensional structures of uPA and pro-uPA, and homology model of the catalytic domain of pro-uPA, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
the enzyme is produced as inactive pro-enzyme, which undergoes several post-translational modifications, the zymogen binds its own receptor uPAR and is cleaved by neighboring, membrane-bound plasmin or other proteases at K158-K159 to produce the active two-chain form held together by a single disulfide bond, further cleavage of pro-uPA at K135-K136 releases the amino-terminal fragment of uPA, overview
proteolytic modification
-
in the 2-chain urokinase, after cleavage of the single-chain proform, the polypeptide chains A and B, light and heavy chains, respectively, are connected by the Cys148-Cys279 disulfide bond. Thrombin hydrolysis provides the mechanism of proteolytic inactivation of uPA cleavage of the Arg156-Phe157 enzyme bond that does not exclude nonproteolytic functioning of such peptide forms
proteolytic modification
-
single-chain uPA is cleaved to the activated two-chain form
proteolytic modification
-
the enzyme is initially synthesized as single-chain proenzyme with an activity that is many orders of magnitude lower than those of the mature enzyme. Proteolytic cleavage of an exposed loop liberates a new amino terminus that inserts into a hydrophobic pocket and forms a stabilizing salt bridge with a ubiquitously conserved aspartate residue, resulting in a conformational change organizing the mature oxyanion hole
proteolytic modification
-
activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa, e.g. LasB, a thermolysin-like metalloprotease, or protease IV, overview. Activation of pro-urokinase by purified LasB, or by the secretomes of Pseudomonas aeruginosa LasB-expressing or LasB-deficient strains
proteolytic modification
-
secretion in inactive forms, and activation by plasmin through proteolytic cleavage, mathematical modeling, overview
proteolytic modification
-
the zymogen form pro-uPA is cleaved to the active two-chain uPA
proteolytic modification
-
uPA is produced and secreted as an inactive single-chain polypeptide, termed pro-uPA, which lacks plasminogen-activating activity. The binding of pro-uPA to urokinase receptor uPAR induces its activation which in turn converts plasminogen to the active serine protease plasmin
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
beta-c-uPA in complex with inhibitor UPA-I1, space group P2(1)2(1)2(1), cell constants a = 53.2 A, b = 54.7 A, c = 82.4 A, beta-c-uPA in complex with inhibitor UPA-I3, space group P2(1)2(1)2(1), cell constants a = 52.9 A, b = 54.7 A, c = 81.4 A, beta-c-uPA in complex with inhibitor UPA-I2, space group P2(1)2(1)2(1), cell constants a = 53.0 A, b = 54.4 A, c = 82.2 A, beta-c-uPA in complex with inhibitor UPA-I5, space group P2(1)2(1)2(1), cell constants a = 53.0 A, b = 54.9 A, c = 82.3 A, beta-c-uPA in complex with inhibitor UPA-I6, space group P2(1)2(1)2(1), cell constants a = 53.5 A, b = 54.8 A, c = 82.4 A, complex by soaking, Ybeta-c-uPA in complex with inhibitor UPA-I6, space group P4(3)2(1)2, cell constants a = 76.7 A, b = 76.7 A, c = 127.5 A, complex by Co-crystallization, beta-c-uPA in complex with inhibitor UPA-I4, space group P4(1)2(1)2, cell constants a = 55.0 A, b = 55.0 A, c = 151.6 A, complex by Co-crystallization
-
crystal structure of the catalytic domain of the recombinant nonglycosylated human uPA, complexed with the inhibitor Glu-Gly-Arg chloromethyl ketone at 2.5 A
-
crystallized by vapor diffusion in hanging drops in complex with 4-iodobenzo[b]thiophene-2-carboxamidine and benzamidine, space group C2, ProteinDataBank accession code 1C5Z for uPA-benzamidine, 1C5Y for uPA-thieno[2,3-b]pyridine-2-carboxamidine
-
in complex with inhibitor N-[(4-chlorobenzyl)sulfonyl]-D-seryl-N-(4-carbamimidoylbenzyl)-L-alaninamide, N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide and N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)glycinamide
-
N-terminal fragment, in complex with urokinase receptor and an antibody against the receptor
-
PAI-1/uPA mutant S195A in a Michaelis complex, hanging drop method, 20C, mixing of equal volumes of protein solution, containing 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, and 150 mM NaCl, and precipitant solution, containing 1.4 M ammonium sulfate and 0.1 M Tris-HCl, pH 7.4, 4 months, the cryoprotectant solution contains 30% glycerol, 1.6 M ammonium sulfate, and 0.1 M Tris-HCl, pH 7.4, X-ray diffraction structure determination and analysis at 2.3 A resolution, molecular replacement
-
purified amino-terminal fragment of urokinase-type plasminogen activator, free and complexed with uPA receptor, lacking the cell-surface anchoring sequence, hanging-drop vapor-diffusion method, room temperature, 0.003 ml of 20 or 8 mg/ml protein, respectively, in 20 mM Tris-HCl, pH 8.0, 150 mM NaCl, is mixed with an equal volume of reservoir solution containing 100 mM Ches, pH 10.5, 1.2 M sodium dihydrogen phosphate, 0.8 M potassium hydrogen phosphate, 200 mM lithium sulfate for the free enzyme or 100 mM Bis-Tris, pH 5.5, 22.5% w/v PEG 3350, 200 mM ammonium sulfate for the enzyme fragment-receptor complex, 1 week, cryoprotection by 15% v/v glycerol, X-ray diffraction structure determination and anaylsis at 1.9-3.3 A resolution, molecular modeling
-
recombinant amino-terminal fragment S1-E143 expressed in Pichia pastoris
-
solution structure of the kringle domain
-
in complex with inhibitors mexiletine and 4-(2-aminoethoxy)-N-(3-chloro-2-ethoxy-5-piperidin-1-ylphenyl)-3,5-dimethylbenzamide
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42
-
10 min, stable up to
29677
55
-
30-60 min, 72-82% loss of activity
29674
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Unstable to dilution
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 0.01 M sodium phosphate buffer, pH 7.0, 0.2 mg/ml enzyme concentration, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
high-molecular weight uPA expressed in SP2/0 cell culture
-
recombinant enzyme
-
recombinant isolated kringle domain UK1 from Pichia pastoris
-
recombinant mutant S195A from Pichia pastoris strain X-33 by nickel affinity chromatography and gel filtration
-
recombinant uPA from S2 cells by immunoaffinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
amino-terminal fragment of human uPA cloned and expressed in Saccharomyces cerevisiae
-
cDNA cloning
-
cloning of low molecular weight uPA, expression in Pichia pastoris
-
DNA and amino acid sequence analysis
-
expression in Escherichia coli
-
expression of mutant enzymes in HEK-293T cells
-
expression of mutant S195A in Pichia pastoris strain X-33
-
expression of the enzyme's kringle domain UK1 in Pichia pastoris
-
expression of wild-type and mutant enzymes in HEK-293T cells
-
functional overexpression of the enzyme in hepatic stellate cells, using an adenoviral vector system
-
mutant C122S expressed in Escherichia coli inclusion bodies, B-chain uPA expressed in S. pastoris
-
semiquantitative reverse transcription PCR expression analysis of uPA and uPAR, overview
-
uPA quantitative real-time RT-PCR expression analysis in oral squamous cell carcinoma, overview
-
macrophage-specific uPA overexpression accelerates atherosclerosis
-
quantitative uPA expression analysis
-
expression using vesicular stomatitis virus G pseudo-typed lentiviruses
-
mutagenesis throughout the single-chain urokinase-type plasminogen activator; mutation affecting the activity
-
expression in S2 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
endogenous miR-193b expression inhibits uPA expression, anti-miR-193b increases uPA expression and increases cell invasion of breast cancer cells. During breast cancer cell metastasis, miR-193b expression is downregulated leading to increased uPA expression
-
inhibition of sphingosine kinase blocks basal expression of uPA and uPAR, as well as glioma cell invasion, however overexpression of sphingosine kinase does not augment sphingosine-1-phosphate receptor-mediated enhancement of uPA activity or invasion
-
inhibitors of p-ERK and p-p38 downregulate uPA in CFPAN-1 and PANC-1 cells, but these inhibitors affect uPAR considerably more than uPA
-
uPA and its endogenous inhibitor PAI-1 are downregulated by grape seed, Vitis ssp., proanthocyanidin extract, both at the RNA and protein levels, due to the extract's antioxidant activity
-
downregulation of uPA and uPAR by early growth response 1, EGR1, forced expression of EGR1 decreases the expression of uPA and urokinase receptor uPAR proteins. uPA activity is decreased 0.49fold by EGR1 in Saos-2 cells
-
efficacy of grape seed extract in downregulating uPA expression and cell migration using highly metastatic androgen-independent PC-3 prostate cancer cells as a model. Grape seed extract inhibits DNA-binding activity of the transcription factor nuclear factor kappa B, which in turn decreases NFkB-dependent uPA transcription. Grape seed extract also inhibits NFkB-dependent urokinase plasminogen activator promoter activity
-
expression of uPA mRNA and enzyme production is increased by the addition of prostaglandin E2, PGE2, in cell lines of lung fibroblasts, although the cell surface uPA level is comparable to that of PGE2 untreated cells, overview
-
lipopolysaccharide induces u-PA expression. TLR-4 and NF-kappaB inhibition ameliorates LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion
-
macrophage inhibitory cytokine-1, MIC-1, is a critical inducer of apoptosis-related gene products such as activated urokinetype plasminogen activator, PLAU, and PLAU receptor, uPAR. Ribotoxic stress agent anisomycin induces MIC-1 gene expression. Gene expression of apoptosis-mediator MIC-1 is enhanced by activating transcription factor 3, ATF-3, via the p38 MAP kinase signaling pathway, and both promoter activity and mRNA stability of MIC-1 gene are up-regulated by ribotoxic anisomycin via the p38 MAP kinase signaling pathway
-
plumbagin induces the enzyme expression in Hep-G2 cells, liver carcinoma cells, also inhibiting the invasion and migration of the cancer cells, overview
-
sphingosine-1-phosphate, S1P, induces expression of uPA and of its receptor uPAr in gliobalstoma multiforme cells. S1P1 receptor overexpression leads to the most dramatic induction of the uPA system and of spheroid invasion, even in the absence of added S1P, while expression of receptors S1P2 and S1P3 does not affect uPA expression, overview
-
TGF-beta1 induces expression of urokinase type plasminogen activator, but the stimulation by TFG-beta1 is inhibited by Spred2
-
uPA is induced by ATP in microglia. The expression and release of uPA is under active regulation in BV2 microglial cells
-
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
-
elevated levels of tissue inhibitor of metalloproteinases-1 , 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
-
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
Mus musculus C57BL/6
-
-
in human endometrial cells, uPA and PAI-1 expression is regulated by steroid hormones such as estradiol, and progesterone. P4 suppresses uPA in epithelial cells and enhances inhibitor PAI-1 expression in both epithelial and stromal cells
-
increase of uPA activity and expression by freezing/thawing process in porcine uterus endometrial epithelium cells. Reactive oxygen species, that occur in high rates in response to the freezing-thawing stimulus, actively participate in the induction of uPA expression in frozen-thawed and in vitro-cultured cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C122S
-
mutant of the serine proteinase domain
E301A
-
site-directed mutagenesis
E301D
-
site-directed mutagenesis
E301H
-
site-directed mutagenesis
H99Y
-
site-directed mutagenesis, the mutation exchanges the human residue H99 for the murine equivalent Y99, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
H99Y/Q192K
-
site-directed mutagenesis, the mutations exchanges the human residues for the murine equivalents, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
K300A
-
site-directed mutagenesis
K300H
-
site-directed mutagenesis
K300W
-
site-directed mutagenesis
P309A
-
60% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
P309D
-
200% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309F
-
500% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309G
-
100% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
P309H
-
400% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309L
-
250% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
P309N
-
150% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
P309R
-
350% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309S
-
50% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
P309T
-
60% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309V
-
80% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
P309W
-
700% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide
R178A/R179A/R181A
-
site-directed mutagenesis, the mutant shows reduced receptor binding
R340A
-
site-directed mutagenesis, the binding of the mutant enzyme to maspin is not affected
S195A
-
site-directed mutagenesis, the mutant contains the catalytically inactive form of the human uPA protease domain
S195A/C122S/N145D
-
inactive variant
S303E
-
site-directed mutagenesis
S356A
-
a catalytically inactive uPA mutant
V41K/H99Y
-
site-directed mutagenesis, the mutations exchanges the human residues for the murine equivalents, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
V41K/H99Y/Q192K
-
site-directed mutagenesis, the mutations exchanges the human residues for the murine equivalents, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
K313A
-
site-directed mutagenesis
additional information
-
reduction of enzyme expression by 53% by stable transfection with antisense/vector construct and by 65% by siRNa transfection results in strong decrease of cellular proliferation activity. Exogenous addition of high-molecular-weight enzyme or enzyme N-terminal fragment lead to increased cell proliferation
additional information
-
deletion of the N-terminal growth factor domain of uPA reduced the affinity for enzyme receptors 2-4fold, depending on the receptor, e.g. VLDLR-I, SorLA, or LRP-1A, and deletion of both the growth factor domain and the kringle reduced the receptor affinity 7fold, overview
additional information
-
functional overexpression of the enzyme in hepatic stellate cells, using an adenoviral vector system, produces downregulation of pro-fibrogenic genes involved in liver fibrosis, and results in a highly specific decrease of TGF-beta expression, and at the same time of genes such as PAI-1, TIMP-1, and collagen type I, which respond to intracellular signals generated by TGF-beta and are involved in perpetuation of fibrogenesis, it also results in upregulation of MMP-3, MMP-2 and MMP-9 activities, overview
additional information
-
the isolated recombinant kringle domain UK1 of uPA shows in vivo antitumor effects in a brain tumor model, systemic administration of purified recombinant UK1 leads to suppression of the growth of a U87 human glioma xenograft, implanted into the brains of male BALB/cSlc nude mice, overview
additional information
-
use of uPA/SCID transgenic mice. Homozygous uPA/SCID mice have a small offspring. Female uPA/SCID mice display a deregulation of ovarian function with an absence of corpus luteum. In male uPA/SCID mice, a decrease of the weight of the testes, epididymis, seminal vesicle, and prostate is measured, associated with an absence of seminal and prostatic secretions and a reduction in testicular sperm production. Transplantation of hepatocytes from mice lacking the uPA transgene results in total repopulation of the livers of uPA/SCID mice and restoration of normal body weight, life span, and reproductive organ function
additional information
-
overexpression of the urokinase-type plasminogen activator N-terminal fragment, uPA ATF, inhibits the combination of uPA receptor and uPA competitively, and the cell invasive migration
additional information
-
transduction of blood monocyte-derived macrophages with uPA-containing adenovirus leads to uPA overexpression. Uptake of the cells into an induced thrombus in mouse leads to increased migration rate of the macrophages and MM6 cells in the thombus, overview. Systemic administration of uPA up-regulated human blood monocyte-derived macrophages reduces thrombus size in an experimental model of venous thrombosis. Adenovirus-uPA transduction increases blood monocyte-derived macrophages fibrinolytic activity by 150fold, and uPAR and PAI-1 production by 1.6fold, it also induces cytokine expression, overview
additional information
-
treatment with uPAR siRNA significantly increases the G0-G1 population by 27% in the CFPAC-1 cells and 20.4% in the PANC-1 cells, compared to control, PAI-2 or uPA siRNA, overview. uPA siRNA treatment reduces cell migration by approximately 25% for CFPAC-1 and 18% for PANC-1 cells. Transfection with PAI-2 siRNA has no effect on cell migration compared to non-silencing siRNA controls
additional information
-
expression of recombinant human uPA in enzyme-ablated mouse livers using adenoviral transfection
additional information
-
generation of an uPA PAI-I docking-site mutant
Y306G
-
site-directed mutagenesis
additional information
-
compensatory skeletal muscle hypertrophy is abrogated in enzyme null mice, overview
additional information
-
enzyme-deficient mice show decreased accumulation of macrophages following muscle injury and severely impaired muscle regeneration, overview
additional information
-
mice deficient for uPA activity fail to induce uPA receptor expression after lipopolysaccharide treatment. In these mice, lipopolysaccharide treatment fails to alter the binding of phosphoglycerate kinase and heterogenous nuclear ribonucleoprotein C with uPA receptor mRNA due to lack of tyrosine phophorylation
additional information
-
mice deficient in uPA show markedly reduced hepatocyte growth factor levels and c-met activation after muscle damage, associated with decreased cell proliferation, myoblast accumulation, and new muscle fiber formation, phenotype, overview. On the other hand, hepatocyte growth factor activity is enhanced at early time points in enzyme inhibitor-deficient PAI-1-/- mice compared with wild-type mice, and the PAI-1-/- animals exhibit accelerated muscle fiber regeneration. Administration of exogenous uPA rescues hepatocyte growth factor levels and muscle regeneration in uPA-/- mice
additional information
Mus musculus C57BL/6
-
compensatory skeletal muscle hypertrophy is abrogated in enzyme null mice, overview, enzyme-deficient mice show decreased accumulation of macrophages following muscle injury and severely impaired muscle regeneration, overview, mice deficient in uPA show markedly reduced hepatocyte growth factor levels and c-met activation after muscle damage, associated with decreased cell proliferation, myoblast accumulation, and new muscle fiber formation, phenotype, overview. On the other hand, hepatocyte growth factor activity is enhanced at early time points in enzyme inhibitor-deficient PAI-1-/- mice compared with wild-type mice, and the PAI-1-/- animals exhibit accelerated muscle fiber regeneration. Administration of exogenous uPA rescues hepatocyte growth factor levels and muscle regeneration in uPA-/- mice
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
-
effect of urokinase-type plasminogen activator on in vitro embryo production. Urokinase-type plasminogen activator added to the 18 h in vitro maturation medium significantly increases embryo development rates
analysis
-
assay of cellular internalization and localization of enzyme:PAI-2 inhibitor complex based on the use of inhibitor labelled with Alexa488 fluorochrome and a polyclonal antibody
analysis
-
optical zymography technique that specifically detects enzyme activity in biological samples via fluorescence emission at 695 nm. Method can efficiently distinguish the active two-chain enzyme from its proenzyme and directly measure enzyme activities in different cancer cell lines
analysis
-
quantification of uPA and inhibitor PAI-1 mRNA expression in breast cancer cell lines as well as in tumor tissue of breast cancer patients by sensitive quantitative real-time PCR assays, based on the LightCycler technology. In breast cancer cell lines, mRNA and antigen values are highly correlated for both uPA and PAI-1 I. Correlations between uPA/PAI-1 mRNA and protein in the breast cancer samples were found to be distinctly weaker or not significant. Quantitative determination of mRNA expression for both factors does not mirror antigen levels in breast cancer tissue
diagnostics
-
expression level of uPA in prostate cancer tissue can be used as a predictor of biochemical recurrence in patients undergoing radical prostatectomy, i.e. strong expression of uPA in addition to a Gleason score, positive surgical margin, and lymph node metastasis
diagnostics
-
uPA is the strongest single indicator of poor prognosis in patients with metastatic breast cancer
diagnostics
-
urokinase-type plasminogen activator is a marker of aggressive phenotype and an independent prognostic factor in mismatch repair-proficient colorectal cancer, overview
drug development
-
the enzyme is an attractive target for the development of small molecule active site inhibitors
drug development
-
uPA is a potential therapeutic target in a variety of pathological conditions, including cancer
drug development
-
complex formation of uPA and uPAR is a target for development of therapeutics
medicine
-
associated with tumor metastasis and invasion, selective inhibitors of uPA may have potential as therapeutically useful drugs for prostate, breast and other cancers
medicine
-
active enzyme promotes tumor progression, activation of enzyme appears as a key step in tumor progression. Inhibition of enzyme with natural or synthetic inhibitors diminishes high intravasating Matrigel invasion in vitro and intravasation and metastasis in vivo
medicine
-
amino-terminal fragment ATF of urokinase exerts an antitumor effect via dual mechanisms: essentially through targeting the uPA-uPAR system via the EGF-like domain and partially through targeting a uPAR-indepedent interaction via the kringle domain
medicine
-
treatment of cancer with small-molecule active-site inhibitors with a C-terminal 4-amindinobenzylamide residue to prevent metastasis. Inhibitor dose of 2 x 1.5 mg/kg/day of inhibitor N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide reduces number of metastases to 4.6% in mice
medicine
-
all patients examined with common variable immunodeficiency had increased plasma levels of soluble uPA receptor with particularly high levels in those with splenomegaly and thrombocytopenia. Plasma uPA levels were also raised in these patients, and both soluble uPA receptor and uPA levels correlated with the monocyte activation marker neopterin. Monocytes from patients with common variable immunodeficiency had increased expression of uPA receptor
medicine
-
either uPA/uPAR interaction, Mac-1 activation, or prevention of its association with uPAR triggers a signaling pathway leading to the inefficient release of HIV from monocytic cells
medicine
-
expression of uPA, its receptor, and of inhibitor PAI-1 is increased in response to Helicobacter pylori, and for uPA, but not the receptor or PAI-1, requires the virulence factor CagE. Helicobacter pylori also stimulates soluble and cell surface-bound uPA activity. It stimulates epithelial cell proliferation, which is inhibited by uPA immunoneutralization and uPA receptor knock-down. Expogenous uPA also stimulates proliferation that is further increased after PAI-1 knock-down
medicine
-
in a severe combined immunodeficient-human mouse model, PC-3 cells are the major source of uPA in the experimental bone tumor. Injection of uPA-silenced PC-3 cells in bone xenografts results in significant reduction of bone tumor burdens and protection of trabecular bones from destruction. The suppressed tumor growth is associated with the level of uPA expression but not with its activity. An increase in the expression of PAI-1, the endogenous uPA inhibitor, is found during in vitro tumor-stromal interactions. Up-regulation of PAI-1 in bone stromal cells and preosteoclasts/osteoblasts is due to soluble factor(s) released by PC cells, and the enhanced PAI-1 expression in turn stimulated PC cell migration
medicine
-
in cancer cell, expression of uPA and uPA receptor underlies a mechanism of stem cell tropism to malignant tumors
medicine
-
in patients with colorectal cancer, the protease antigen levels are significantly higher compared with other groups. At the time of clinical detection proteases cathepsin B, cathepsin L and urokinase-type plasminogen activator and its inhibitor are more sensitive indicators for colorectal cancer than commonly used tumor markers. Determination of cathepsin B, cathepsin L and urokinase-type plasminogen activator and its inhibitor have a major prognostic impact in patients with colorectal cancer
medicine
-
in sputum derived from patients with house dust mite allergic asthma, the medium concentration of uPA is significantly greater than in healthy control patients. The sputum concentration of uPA correlates with sputum total cell count and with logarithmically transformed exhaled nitric oxide concentration, but not with FEV1 or bronchial reactivity to histamine. Tge effect of uPA seems to be independent of its fibrinolytic activity
medicine
-
quantification of uPA and inhibitor PAI-1 mRNA expression in breast cancer cell lines as well as in tumor tissue of breast cancer patients by sensitive quantitative real-time PCR assays, based on the LightCycler technology. In breast cancer cell lines, mRNA and antigen values are highly correlated for both uPA and PAI-1 I. Correlations between uPA/PAI-1 mRNA and protein in the breast cancer samples were found to be distinctly weaker or not significant. Quantitative determination of mRNA expression for both factors does not mirror antigen levels in breast cancer tissue
medicine
-
silencing of transmembrane protein Notch1 expression by siRNa inhibits invasion of human prostate cancer cells by inhibiting the expression of matrix metalloproteinase-9 and uPA
medicine
-
the levels of uPA and uPA receptor in patients with acute or chronic hepatitis B significantly exceeds those in healthy controls. Patients with severe chronic hepatitis B have significantly higher levels of uPA and uPA receptor than those with moderate and mild chronic disease and those with acute hepatitis B. The plasma uPA and uPA receptor levels markedly increase in the acute stage and dramatically decrease in the remission stage, but in all stages levels exceede those in healthy subjects. The concentration of plasma uPA receptor is positively correlated with prothrombin and total bilirubin
medicine
-
the overexpression of uPA in Quebec platelet disease emerges with megakaryocyte differentiation, without altering the expression of flanking genes. uPA is costored with-granule proteins prior to their proteolysis in Quebec platelet disease
medicine
-
uPA, seprase and pipeptidylaminopeptidase IV immunoreactivity is found in dysplastic and cancer cells as well as in stromal cells adjacent to dysplasia and cancer sites, but not in normal epithelium. There is a significant association between uPA expression and sex, tumor size and histological classification in carcinomas. Squamous cell carcinoma lines display higher levels of uPA, seprase and dipeptidylaminopeptidase IV than normal esophageal epithelial cell lines
medicine
-
macrophages, recruited into venous thrombi, can be used to target uPA gene constructs to the thrombus after systemic administration
medicine
-
co-operation between TIMP-1 and host uPA suggests that therapies, simultaneously interfering with pro- and anti-proteolytic pathways may be beneficial for patients with metastatic disease
pharmacology
-
rapid, sensitive and selective method for detection of uPA activator UK-356202 in human plasma using column-switching HPLC and fluorescence detection. The limit of detection is 20 pg/ml, and the method is linear over a 100-fold concentration range
pharmacology
-
Treatment of nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 with TX-1877, irradiation or TX-1877 with irradiation results in significant inhibition of matrix metalloproteinase-9 and uPA. Treatments also inhibit the para-aortic lymph node metastasis, however, do not prolong the survival in orthotopic model. In the subcutaneous model, tumors treated with TX-1877 and irradiation show significant reductions in volume
pharmacology
-
uPA blocking antibodies may not be indicated for cancer growth inhibition strategies, but may serve as valuable tools for the implementation of pharmacodelivery strategies against a variety of different tumors
medicine
-
after infection with staphylococci, level of metabolically active enzyme is unaltered in plasma but significantly decreased in kidney homogenate. Enzyme acts as endogenous antibacterial substance. Decrease in enzyme level in infected organs may be due to dramatically increased production of plasminogen activator inhibitor type I
medicine
-
amino-terminal fragment ATF of urokinase exerts an antitumor effect via dual mechanisms: essentially through targeting the uPA-uPAR system via the EGF-like domain and partially through targeting a uPAR-indepedent interaction via the kringle domain
medicine
-
in mice model for kidney ischemia reperfusion injury, deficiency for uPA receptor, but not uPA protects from ischemia reperfusion injury. In the allogenic kidney transplant model, uPA receptor but not uPA deficiency of the allograft causes superior recipient survival and strongly attenuates loss of renal function. uPA receptor-deficient allografts show reduced generation of reactive oxygen species and apoptosis. Neutrophil and monocyte/macrophage infiltration is strongly attenuated and up-regulation of the adhesion molecule ICAM-1 is completely abrogated in uPA receptor-deficient allografts
medicine
-
possible involvement of uPA in natural killer cell-mediated immune surveillance and tumor escape. Addition of uPA to natural killer cell receptor Ly49E positive adult and fetal natural killer cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively
medicine
-
co-operation between TIMP-1 and host uPA suggests that therapies, simultaneously interfering with pro- and anti-proteolytic pathways may be beneficial for patients with metastatic disease
medicine
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brain tissue of thermally injured rats displays an increase in the brain water content and the presence of Evans blue, temporally associated with an increased expression of endogenous tPA and uPA. Peripheral thermal injury does induce an increase in the permeability of the blood brain barrier
medicine
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study on cocaine-induced conditioned-place preference in rats with bilateral intra-accumbens injections of uPA-expressing lentiviral vectors. Overexpression of uPA in the nucleus accumbens significantly augments cocaine-induced place preference. Reinstatement with a low dose of cocaine produces significantly greater preference to the cocaine-associated context. Once cocaine-induced conditioned-place preference has been established, and the preference extinguished, reinstatement induced by a priming dose of cocaine is facilitated by uPA. Inhibition of tuPA expression abolishes the augmented acquisition produced by overexpression of uPA but not the expression of the cocaine-induced conditioned-place preference. When uPA is inhibited during the acquisition phase, animals no longer demonstrate place preference for the environment previously paired with cocaine. B428, a specific uPA inhibitor does not affect drug reinstatement after extinction if uPA has been activated during acquisition. Cocaine-induced conditioned-place preference and reinstatement may be dependent on active extracellular uPA
medicine
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uPA promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury
medicine
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induction of lateral fluid percussion brain injury results in up-regulation of uPA and ERK mitogen-activated protein kinase. uPA contributes to the impairment of sodium nitroprusside and PGE2-mediated cerebrovasodilatation through activation of low-density lipoprotein receptor and ERK mitogen-activated protein kinase