Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.62733169
Furthermore , uPA exerts its action by binding to a membrane bound receptor ( uPAR ) . 0.62733169^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :1.2287824
We show that uPAR with bound uPA : PAI 1 is capable of entering cells in a clathrin independent process . 1.2287824^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.56037109
Urokinase ( uPA ) interacts with its receptor ( uPAR ) to promote proteolysis and tumor migration , functions of potential importance in the pathogenesis of malignant mesothelioma . 0.56037109^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :1.0278413
The activation of pro uPA to the active two chain uPA is accelerated with uPAR bound pro uPA and is achieved by plasmin and proteases of other classes like cathepsins G and L . uPAR bound uPA is susceptible to inhibition by its specific inhibitors ( PAI 1 , PAI 2 , and PN 1 ) . uPA PAI 1 and uPA PN 1 complexes , but not free uPA , are readily internalized and degraded through a mechanism that involves the multiligand receptors alpha 2 macroglobulin receptor / low density lipoprotein receptor associated protein ( alpha 2 MR ) and epithelial glycoprotein 330 ( gp 330 ) . 1.0278413^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.73902333
In conclusion , these results demonstrate that rec uPAR 277 can function as a scavenger for uPA in vitro by inhibiting proliferation and invasion of human cancer cells . . 0.73902333^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.56414028
Downregulation of cell surface uPAR molecules in U 937 cells was detected by cytofluorimetric analysis after uPA PAI 1 and uPA PN 1 incubation for 30 min at 37 degrees C ; this effect was blocked by preincubation with the ligand of LRP / alpha 2 MR , RAP ( LRP / alpha 2 MR associated protein ) , known to block the binding of the uPA complexes to LRP / alpha 2 . 0.56414028^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :1.5812335
Urokinase type plasminogen activator ( uPA ) is synthesized as single chain protein ( scuPA ) with little intrinsic activity . scuPA is activated when it is converted to two chain urokinase ( tcuPA ) by plasmin or when it binds as a single chain molecule to its cellular receptor ( uPAR ) . 1.5812335^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.50510534
In keratinocytes , uPA binds to a specific cell surface receptor for uPA ( uPA R = CD 87 ) in an autocrine manner . 0.50510534^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.71140119
A specific cell surface receptor ( uPAR ) binds uPA and strongly enhances plasmin generation , and the amount of uPAR in the tumor tissue might therefore be a rate limiting factor in the extracellular proteolysis involved in tumor invasion . 0.71140119^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.54694639
Furthermore , blocking the interaction of endogenous uPA with uPAR using anti NTF antibodies significantly inhibited proliferation . 0.54694639^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.89983631
We used the patch clamp technique to demonstrate that urokinase ( uPA ) binds to uPAR and thereby stimulates Ca ( 2+ ) activated K+ channels in U 937 cells . uPA transiently increased K+ currents within 30 s . 0.89983631^^^ Taken together , our findings indicate that uPA binds to uPAR and stimulates the production of Ins ( 1 , 4 , 5 ) P 3 via a G protein and phospholipase C dependent mechanism . 0.7693273^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.59699062
Moreover , the system also supports cell migration and invasion by plasmin independent mechanisms , including multiple interactions between uPA , uPAR , PAI 1 , extracellular matrix proteins , integrins , endocytosis receptors , and growth factors . 0.59699062^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.87358591
Here we investigated whether direct interaction between uPAR , a glycosyl phosphatidylinositol anchored protein , and LRP , a transmembrane receptor , is required for clearance of uPA : PAI 1 , regeneration of unoccupied uPAR , activation of plasminogen , and the ability of HT 1080 cells to invade extracellular matrix . 0.87358591^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.51039076
Soluble , recombinant suPAR was added and the interaction of SP uPA with suPAR verified by reaction with monoclonal antibody HD13 . 1 directed to uPAR , followed by a cyan dye ( cy 5 ) labeled antibody directed against mouse IgG . 0.51039076^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.54465489
We demonstrate a tight connection between uPA regulated uPAR oligomerization and high affinity binding to immobilized vitronectin . 0.54465489^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.63611518
The urokinase receptor ( uPAR , CD 87 ) as a target for tumor therapy : uPA silica particles ( SP uPA ) as a new tool for assessing synthetic peptides to interfere with uPA / uPA receptor interaction . 0.63611518^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.67617742
Strong clinical and experimental evidence has accumulated that the cell surface interaction of uPA with uPAR facilitates extravasation and intravasation of cancer cells by regulating local proteolysis and attachment of the cells to components of the extracellular matrix . 0.67617742^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.85332377
However , when uPA was added to corneal fibroblasts before fixation , a dynamic association between uPAR and the actin cytoskeleton was revealed : the uPA / uPAR complex was immunodetected throughout the surface of the plasma membrane in the form of dispersed small aggregates ( 0 . 05 microm 2 ) . 0.85332377^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :1.0557596
Cells secrete uPA as a single chain molecule ( scuPA ) . scuPA can be activated by proteolytic cleavage to a 2 chain enzyme ( tcuPA ) . scuPA is also activated when it binds to its receptor ( uPAR ) . 1.0557596^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.53450247
The amino terminal fragment ( ATF ) of uPA is the major receptor binding determinant in suPAR and binds to suPAR with nanomolar affinity , indistinguishable from membrane bound uPAR . 0.53450247^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.66847293
It is also known that uPA binds to uPAR and activates the RAS extracellular signal regulated kinase ( ERK ) signaling pathway . 0.66847293^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :1.4651378
Initiation of plasminogen activation on the surface of monocytes expressing the type 2 transmembrane serine protease matriptase . uPA ( urokinase type plasminogen activator ) activates plasminogen with high efficiency when bound to its cellular receptor uPAR , but only after a prolonged lag phase during which generated plasmin activates pro uPA . 1.4651378^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.5762864
Furthermore , the CPp alpha 5 beta 5 integrin interaction enhances F actin enriched protrusions and cell migration induced by the well established interaction between the uPAR binding peptide ( GFDp , residues 12 32 ) of uPA and uPAR . 0.5762864^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.74885578
Binding parameters [ association rate ( kass ) and dissociation rate ( kdiss ) constants , and affinity constants ( KA = kass / kdiss ) ] for the interaction between urokinase type plasminogen activator ( u PA ) and its substrate plasminogen , its inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) and its receptor ( u PAR ) , were determined by real time biospecific interaction analysis ( BIA ) . 0.74885578^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.52779541
Plasminogen activation is regulated by the interaction between urokinase type plasminogen activator ( uPA ) and its specific glycolipid anchored cell surface receptor ( uPAR ) . uPAR is composed of three homologous domains and is the only multi domain member of the Ly 6 family of glycolipid anchored membrane proteins . 0.52779541^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.57453163
Urokinase type plasminogen activator ( uPA ) is involved in generating the proteolytic activity necessary for invasive processes , and is dependent on binding to its specific cellular receptor ( uPAR ) for efficient function . 0.57453163^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.68991067
The association of urokinase type plasminogen activator ( uPA ) with its receptor ( uPAR ) influences various biologic functions , including cell migration , angiogenesis , differentiation , and wound healing . 0.68991067^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.6411666
Inhibition of the interaction of urokinase type plasminogen activator ( uPA ) with its receptor ( uPAR ) by synthetic peptides . 0.6411666^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.50655665
Urokinase type plasminogen activator ( uPA ) binds to a plasma membrane receptor ( uPAR ) that localizes plasmin generation to the cell environment . 0.50655665^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.51070325
The urokinase type plasminogen activator ( uPA ) interacts with its receptor ( uPAR ) to promote proteolysis as well as cell proliferation and migration . 0.51070325^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.51617102
The urokinase type plasminogen activator ( uPA ) interacts with its receptor ( uPAR ) to promote local proteolysis as well as cellular proliferation and migration . 0.51617102^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.55313824
The serine protease urokinase type plasminogen activator ( uPA ) interacts with a specific receptor ( uPAR ) on the surface of various cell types , including tumor cells , and plays a crucial role in pericellular proteolysis . 0.55313824^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.75761362
The high affinity interaction between the urokinase type plasminogen activator ( uPA ) and its glycolipid anchored cellular receptor ( uPAR ) promotes plasminogen activation and the efficient generation of pericellular proteolytic activity . 0.75761362^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.64966656
The N terminal domain or ATF binds to a Urokinase receptor ( uPAR ) on the cell surface and the C terminal serine protease domain , then , activates plasminogen to plasmin , beginning a cascade of events leading to the progression of cancer . 0.64966656^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.53851007
We conclude that activation of u PAR after interaction with u PA at the cell surface initiates a transmembrane signal , most likely in conjunction with other still unknown protein ( s ) . 0.53851007^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.71049696
Rather , pericellular molecular and functional interactions between u PA , u PAR , PAI 1 , extracellular matrix proteins , integrins , endocytosis receptors and growth factors appear to allow temporal and spatial re organizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion . 0.71049696^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.52317932
The production of urokinase type plasminogen activator ( u PA ) by synovial cells and chondrocytes and the subsequent interaction of u PA with its membrane receptor ( u PAR ) is under the control of a variety of growth factors and cytokines released within the inflamed joints . 0.52317932^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.56806574
Interaction between u PA and its receptor appears to be mandatory for the angiogenic effect of u PA because monoclonal antibodies anti u PA and anti u PA receptor ( u PAR ) blocked the proangiogenic effects of u PA at the endothelial cell level . 0.56806574^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.70070935
The balance between u PAR bound u PA and inhibitors modulate a pericellular proteolytic activity able to give `` stop and go ' ' signals to invading cells . 0.70070935^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.9879386
Plasmin degrades fibrin into soluble fibrin degradation products , by two physiological plasminogen activators ( PA ) , the tissue type PA ( t PA ) and the urokinase type PA ( u PA ) . t PA mediated plasminogen activation is mainly involved in the dissolution of fibrin in the circulation . u PA binds to a specific cellular receptor ( u PAR ) , resulting in enhanced activation of cell bound plasminogen . 0.9879386^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Interleukin 6 ( IL 6 ) had no effect . uPA receptor ( uPAR ) mRNA levels were also upregulated . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of uPA to a specific cell surface receptor ( uPAR ) is a key step in this process . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
High alpha ( 5 ) beta 6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Both uPAR positive cell populations also express uPA immunoreactivity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Several observations indicated the kringle facilitates the binding of uPA to uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Unexpectedly , PN 1 was found to increase the association between VN and uPAR in the presence of enzymatically active uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Serp 1 inhibition of monocyte migration was lost in uPA receptor ( uPAR ) deficient mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( CD 87 ) is a pleiotropic molecule . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
High levels of urokinase type plasminogen activator receptor ( uPAR ) are expressed in various types of cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
UVB increases urokinase type plasminogen activator receptor ( uPAR ) expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Occupancy of uPAR with urokinase type plasminogen activator further enhanced the cell adhesion to fibrinogen . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PURPOSE : The urokinase type plasminogen activator receptor ( u PAR ) contributes to colon cancer invasion and metastases . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We review the leading role of u PA and its receptor ( u PAR ) in cartilage degradation . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The u PA in the milk leukocytes was shown to be bound to urokinase receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase ( u PA ) to its cell surface receptor ( u PAR ) is critical for tumor cell invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Trace staining was found for u PA receptor ( u PAR ) in differentiated tumor cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Soluble HGF receptor ( MET ) and soluble u PAR ( u PA receptor ) inhibited the scHGF cleavage . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the kidney , u PA and its receptor ( u PAR ) were almost exclusively expressed at the apex of collecting duct cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The role of the urokinase receptor ( uPAR ) in the internalization of the urokinase plasminogen activator inhibitor type 1 ( uPA . ^^^ First , exploiting the species specificity of uPA binding , we show that mouse LB 6 cells ( that express a mouse uPAR ) were unable to bind or degrade the human uPA . ^^^ On the other hand , LB 6 clone 19 cells , which express a transfected human uPAR , degraded uPA . ^^^ PAI 1 internalization / degradation is mediated by uPAR , inhibition of uPA . ^^^ Three different treatments , competition with the agonist amino terminal fragment of uPA , treatment with a monoclonal antibody directed toward the binding domain of uPAR or release of uPAR from the cell surface with phosphatidylinositol specific phospholipase C completely prevented uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase type plasminogen activator ( uPA ) to its specific cell surface receptor ( uPAR ) localises the proteolytic cascade initiated by uPA to the pericellular environment . ^^^ Inhibition of uPA activity or prevention of uPA binding to uPAR might have a beneficial effect on disease states wherein this activity is deregulated , e . g . cancer and some inflammatory diseases . ^^^ To this end , a bifunctional hybrid molecule consisting of the uPAR binding growth factor domain of uPA ( amino acids 1 47 ; GFuPA ) at the N terminus of plasminogen activator inhibitor type 2 ( PAI 2 ) was produced in Saccharomyces cerevisiae . ^^^ GFuPA PAI 2 competed with uPA , the N terminal fragment of uPA and a proteolytic fragment of uPA ( amino acids 4 43 ) in cell binding experiments , indicating that the molecule bound to the cells via uPAR . ^^^ Hence , both the uPA inhibitory and uPAR binding domains of the hybrid molecule were functional , demonstrating the feasibility of the novel concept of introducing an unrelated , functional domain onto a member of the serine protease inhibitor superfamily . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Moreover , it was possible to remove membrane bound uPA by treating the cells with phosphatidylinositol specific phospholipase C , suggesting that rat uPAR , like its human counterpart , is linked to the membrane by a glucosyl phosphatidylinositol anchor . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cellular urokinase type plasminogen activator ( uPA ) receptor ( uPAR ) is a glycolipid anchored membrane protein thought to be involved in pericellular proteolysis during cell migration and tumor invasion . ^^^ Under normal conditions , we find no evidence for any shedding or secretion of a soluble uPA binding counterpart to human uPAR in plasma . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Colonies inducing lysis ( clone C+ and H+ ) or no lysis ( clones B and M ) were isolated and tested for mRNA levels of uPA , tPA , uPA receptor ( uPAR ) and the 3 PA inhibitors ( PAI ) , PAI 1 , PAI 2 and protease nexin 1 . ^^^ Receptor bound uPA activity was found to be considerably higher in lysis inducing than in non lysing clones and the activity was dependent on neutralization by PAI 1 rather than on the level of uPAR mRNA . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PAI 1 , like uPA and its amino terminal fragment , bound to the urokinase receptor ( uPAR ) . ^^^ Degradation of uPAR bound 125I uPA . ^^^ PAI 1 was 3 4 fold enhanced as compared with uncomplexed uPAR bound uPA . ^^^ This is taken as evidence for mediation of internalization and degradation of uPAR bound uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have found that urokinase ( uPA ) can cleave its receptor between domains 1 and 2 generating a cell associated uPAR variant without ligand binding properties . ^^^ Addition to the culture medium of an anticatalytic monoclonal antibody to uPA inhibited the formation of the uPAR ( 2+3 ) , indicating that uPA is involved in its generation . ^^^ Purified uPAR can be cleaved directly by uPA as well as by plasmin . ^^^ The uPA catalyzed cleavage does not require binding of the protease to the receptor through its epidermal growth factor like receptor binding domain , since low molecular weight uPA that lacks this domain also cleaves uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Occupancy of the cancer cell urokinase receptor ( uPAR ) : effects of acid elution and exogenous uPA on cell surface urokinase ( uPA ) . ^^^ Following acid elution , cell surface uPA activity was restored after 30h in culture suggesting either de novo synthesis or release of pre formed uPA with subsequent secretion and binding to uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To test whether uPA produced by one cell can , in a paracrine fashion , affect the invasive capacity of a receptor expressing cell , we transfected LB 6 mouse cells with human uPA ( LB 6 [ uPA ] ) , or human uPA receptor cDNA ( LB 6 [ uPAR ] ) . ^^^ The LB 6 ( uPAR ) cells expressed on their surface approximately 12 , 000 high affinity ( Kd 1 . 7 10 10 ( 10 ) M uPA binding sites per cell . ^^^ Unlabeled LB 6 ( uPA ) and 125 IUdR labeled LB 6 ( uPAR ) cells were coinoculated onto experimentally wounded and resealed CAMs and their invasion was compared to that of homologous mixtures of labeled and unlabeled LB 6 ( uPAR ) or LB 6 ( uPA ) cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of the uPAR cDNA in mouse cells confirms that the clone is complete and expresses a functional uPA binding protein , located on the cell surface and with properties similar to the human uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of uPA , uPA receptor ( uPAR ) , and PAIs is regulated by growth factors , oncogenes , and other effector molecules . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The properties of the uPA receptor ( uPAR ) and the localization and distribution of uPA in tumor cells and tissues suggest that the uPA / uPAR interaction may be important in regulating extracellular proteolysis dependent processes ( e . g . , invasion , tissue destruction ) . ^^^ PMA treatment also causes a decrease in the affinity of the uPAR for uPA , thus uncovering another way of regulating the interaction between uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It has been posited that the GPI anchor facilitates clearance of uPAR bound complexes between two chain urokinase ( tcuPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) by the alpha 2 macroglobulin receptor ( alpha 2MR ) which permits re expression of unoccupied uPA receptors on the cell surface . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) activity has previously been shown to play a role in migration of cells into basement membranes , and it has been proposed that uPAR also is involved in this process . uPA is known to be internalized and degraded after complex formation with the inhibitor PAI 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A human epithelial cell line , WISH , and a mouse cell line , LB 6 uPAR , transfected with the human urokinase receptor ( uPAR ) , both expressed high affinity uPAR but undetectable levels of urokinase ( uPA ) . ^^^ To test this hypothesis , we carried out a solid phase capture of uPAR from WISH cell lysates using either antibodies against uPAR or pro uPA adsorbed to plastic wells , followed by in vitro phosphorylation of the immobilized proteins . ^^^ These results strongly suggest that uPAR serves not only as an anchor for uPA but participates in a signal transduction pathway resulting in a pronounced biological response . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Assays for urokinase plasminogen activator type ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and the urokinase receptor ( uPAR ) were conducted . ^^^ The cell line produces uPA and PAI 1 , and also expresses uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The glycosylphosphatidylinositol ( GPI ) anchored membrane protein urokinase plasminogen activator receptor ( uPA R ; CD 87 ) is one of the key molecules involved in migration of leukocytes and tumor cells . uPA bound to uPA R provides the cell proteolytic potential used for degradation of extracellular matrix . uPA R is also involved in induction of cell adhesion and chemotaxis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Northern analysis of poly A+RNA prepared from cultured human mesangial cells revealed mRNA for tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and uPA receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The distributions of urokinase and tissue plasminogen activators ( uPA , tPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) were studied immunohistochemically in two subsets of colorectal adenocarcinomas with low and high aggressiveness , respectively : nine Dukes ' stage A tumors with additional other good prognostic markers and 13 Duke ' s stage C tumors with also other poor prognostic markers ( referred to as Dukes ' stage A and Dukes ' stage C tumors ) . ^^^ Both tumor groups showed accumulations of uPA , uPAR , and PAI 1 at the tumor host interface compared with the location within the tumor epithelium and the adjacent normal mucosa and muscularis propria ( all P < . 05 ) . ^^^ This may indicate that uPA in more aggressive tumors exceeds the inhibitory capacity represented by PAIs , resulting in enhanced tissue destructive potential that promotes tumor invasion . uPA and uPAR antigen levels and the uPA / PAI 1 ratio at the tumor host interface appeared to be related to tumor aggressiveness in colorectal cancer . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase type plasminogen activator ( uPAR ) may contribute to the invasive and metastatic capacity of tumor cells by focusing the serine protease urokinase type plasminogen activator ( uPA ) to the cell surface . uPA activates plasminogen to plasmin which in turn degrades extracellular matrix proteins or activates other proteases . ^^^ Soluble uPAR , synthesized by CHO cells ( corresponding to amino acids 1 277 of human uPAR ) , was isolated by ligand ( uPA ) affinity chromatography . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The presence of mRNA for the uPA receptor ( uPAR ) has been demonstrated in these cells and steady state levels shown to be greatly enhanced , the response being rapid and sustained for at least 24 hours . mRNA for plasminogen activator inhibitor 1 ( PAI 1 ) was modulated in a biphasic manner , with inhibition of the constitutive level apparent at 4 hours of treatment and stimulation apparent at 12 hours and longer , while PAI 1 protein , measured by an ELISA assay for rat PAI 1 , was diminished over this period . ^^^ Although it was not possible to measure uPAR number and affinity it seems likely that elevated uPAR mRNA would translate into increased uPARs which would localize the increased uPA activity to the pericellular region . tPA mRNA and activity were also increased transiently with the activity inhibited with prolonged incubations , apparently by PAI 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , bound to its receptor ( uPAR ; CD 87 ) facilitates plasmin formation , which promotes matrix proteolysis . ^^^ Polymorphonuclear leukocytes ( PMNs ) are critical to the inflammatory response and express both uPA and CD 87 . ^^^ To determine whether uPA and CD 87 are required for PMN chemotaxis , PMNs were pretreated with an anti CD 87 monoclonal antibody ( mAb ) , a neutralizing anti uPA mAb , or uPA . ^^^ PMN chemotaxis was profoundly suppressed by the anti CD 87 mAb but was unaffected by anti uPA mAb or uPA . ^^^ We conclude that CD 87 plays a crucial role in PMN chemotaxis in vitro that is independent of uPA enzyme activity but may be related to the ability of CD 87 to interact with CR3 . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These mice provide a means to test the proposed function of uPA / uPAR in wound repair , atherogenesis , and tumor cell invasion in vivo . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase type plasminogen activator ( uPAR ) is an integral membrane protein that specifically binds urokinase type plasminogen activator ( uPA ) and plays a crucial role in cell surface plasmin generation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The uPA receptor , uPAR , is a cell surface protein which plays an important role in the localization and regulation of these processes . ^^^ A few reagents have been identified which are capable to inhibit the interaction between uPAR and uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Butyrate was found to induce a rapid and transient increase in plasminogen activator inhibitor type 1 ( PAI 1 ) mRNA while concomitantly suppressing the constitutive production of both urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) mRNA transcripts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
By immunohistochemistry , we studied the expression of PAs ( tPA and uPA ) , their major physiological inhibitor ( PAI 1 ) , and a receptor for uPA ( uPAR ) in human coronary arteries with either pure fibrointimal proliferation ( n = 15 ) or developed atherosclerotic plaques ( n = 10 ) . ^^^ Overall , the degree of staining showed the following rank order : PAI 1 > tPA > uPAR > uPA . ^^^ However , the ratio of intimal to medial expression of tPA ( P = . 001 ) and uPAR ( P = . 004 ) was significantly increased in atherosclerotic arteries , with a similar trend for uPA ( P = . 069 ) but not for PAI 1 ( P = . 73 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Both uPAR and its ligand , uPA , were present in caveolae enriched low density Triton 10 100 insoluble complexes , as shown by immunoblotting . ^^^ Thus , caveolae promote efficient cell surface plasminogen activation by clustering uPAR , uPA , and possibly other protease receptors in one membrane compartment . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we report that VEGF increases the high affinity binding of uPA to the same cells and that this binding is prevented by a peptide corresponding to the uPA receptor ( uPAR ) binding growth factor like domain of uPA . ^^^ Ligand cross linking , ligand blotting , and uPA Sepharose affinity chromatography revealed an increase in a cell surface uPA binding protein that corresponds to the uPAR on the basis of its affinity for uPA , M ( r ) of 50 , 000 55 , 000 , and phosphatidylinositol specific phospholipase C sensitivity . ^^^ By Scatchard analysis , VEGF increased the number of uPAR molecules by 2 . 8 3 . 5 fold and concomitantly decreased their affinity for uPA . ^^^ Taken together , these findings demonstrate that VEGF induced angiogenesis is accompanied by increased uPAR expression and uPA activity on the endothelial cell surface . ^^^ These observations are consistent with the notion that the uPA uPAR interaction facilitates cellular invasion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A cell surface receptor for uPA ( uPAR ) is attached to the cell membrane by a glycosyl phosphatidylinositol anchor . ^^^ Binding of uPA to uPAR leads to an enhanced plasmin formation and thereby an amplification of pericellular proteolysis . ^^^ Binding of pro uPA by uPAR in plasma may interfere with the appropriate binding of pro uPA to cell bound uPAR and therefore inhibit cell associated plasmin generation and fibrinolysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Increased levels of uPAR have been found in primary malignant brain tumor tissues , especially highly malignant glioblastoma , and , to a lesser degree , in malignant astrocytomas , suggesting that this receptor might be involved in efficient activation of pro uPA and confinement of uPA activity on the cell surface of invading brain tumors . ^^^ These results imply that uPAR is involved in plasmin catalyzed proteolysis during glioma invasion and that interference with the uPA : uPAR interactions could constitute a novel approach for developing therapeutic strategies to counteract invasion of brain tumors . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously characterized a specific cell surface receptor for uPA ( uPAR ) which strongly enhances the catalytic activity of uPA and is expressed during mammary cancer invasion . ^^^ Both free uPAR and uPAR in complex with uPA is detected . ^^^ In order to find a suitable buffer for extraction of various components of the uPA system from breast cancer tissue , we tested buffers which previously have been used for optimal extraction of estrogen receptor ( A ) , uPA ( B ) , and uPAR ( C ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In contrast , the uPA receptor ( uPAR ) dramatically increases , beginning within 1 minute after PHx . ^^^ These findings imply that both uPA and uPAR are involved in activating endogenous HGF in the regenerating livers of animals that underwent PHx . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) is a serine protease involved in cancer invasion and metastasis . uPA mediates its action while attached to a membrane bound receptor ( uPAR ) . ^^^ In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers . uPAR levels , however , do not correlate with other components of the plasminogen activator system such as tissue type plasminogen activator ( t PA ) , PAI 1 or PAI 2 . ^^^ However , as a prognostic marker in breast cancer , uPAR was not as strong as uPA . ^^^ Our results are consistent with data from model systems suggesting that both uPA and uPAR are necessary for metastasis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase plasminogen activator ( uPA R , CD 87 ) is a glycosylphosphatidylinositol ( GPI ) anchored 50 to 65 kD glycoprotein that , by regulating membrane associated plasmin activity , may facilitate the invasion of inflammatory and malignant cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Transcription and expression of the urokinase ( uPA ) receptor ( uPAR ) are strongly stimulated by PMA . ^^^ Sensitivity of U 937 cells to uPA saporin , a toxin conjugate that reguires binding to uPAR for killing activity , was also markedly decreased . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , which binds to cells via a specific receptor ( uPAR ) , participates in pericellular proteolysis during leukocyte migration . ^^^ To test the functional interactions of CR 3 and uPAR , we have examined the ability of uPA to elicit changes in cytosolic calcium levels of normal neutrophils , neutrophils from a leukocyte adhesion deficiency ( LAD ) patient , and 3T3 transfectants expressing CR 3 , uPAR , or both . ^^^ The uPA dependent calcium rise was inhibited by mAb directed against either CR 3 or uPAR and required intact uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) binds with high affinity to a specific cell surface glycosyl phosphatidyl inositol ( GPI ) anchored receptor , the urokinase receptor ( uPAR ) . ^^^ The present study investigated whether pro uPA bound to uPAR is still susceptible to inactivation by thrombin in the presence or absence of TM . ^^^ Rec uPAR 277 efficiently inhibited the thrombin mediated inactivation of pro uPA up to 90 % in a concentration dependent manner . ^^^ The inactivation kinetics of pro uPA by thrombin ( no TM added ) in the presence of an excess of rec uPAR 277 could not be determined since virtually no inactivation occurred . ^^^ Our data suggest that pro uPA once bound to uPAR , is significantly protected from inactivation by thrombin . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The effects of butyrate on the modulation of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) mRNAs were studied . ^^^ Nuclear run on transcription assays indicated that uPA mRNA was modulated by butyrate at the transcriptional level but the uPAR gene was regulated at both transcriptional and post transcriptional levels in the presence or absence of TNF alpha . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present study evaluate both the expression and release of PAs ( uPA and tPA ) and PAIs ( PAI 1 and PAI 2 ) from cultured cells , and also the expression of uPA receptor ( uPAR ) . ^^^ Immunocytochemistry showed that PAs , PAIs and uPAR were present to different extents on the surface of colon carcinoma cells ( Caco 2 , HT 29 ) , malignant melanoma cells ( LOX ) and normal fibroblasts . uPA immunoreactivity was intermediate in Caco 2 , HT 29 and LOX and weak in the fibroblasts . tPA immunoreactivity was intermediate in Caco 2 and LOX and weak in HT 29 and fibroblasts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The conjugate formed with this unknown component had a much higher molecular weight ( apparent M ( r ) 250 , 000 300 , 000 ) than the complex of pro uPA and the urokinase plasminogen activator receptor ( uPAR ) . ^^^ The conjugate was recognized by antibodies against uPA but not by anti uPAR antibodies . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have compared the histological localization of urokinase plasminogen activator ( uPA ) and urokinase plasminogen activator receptor ( uPAR ) in breast cancer sections using a panel of monoclonal antibodies . ^^^ First , the ability of six different anti uPA monoclonal antibodies to recognize pro uPA , uPA , and in vitro formed complexes of uPA with either soluble uPAR or with plasminogen activator inhibitor type 1 was compared . ^^^ Then the reactivity of the anti uPAR antibodies was tested , and the occurrence of an uPA receptor of about M ( r ) 55 , 000 in samples from breast carcinoma was assessed by immunoprecipitating the uPA receptor from an in vitro 125I labeled tumor extract . ^^^ In conclusion , these results show that occupied uPA receptors are definitely present on the membrane of epithelial tumor cells and suggest the occurrence of uPA uPAR dependent proteolytic activity on the surface of breast cancer cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : The binding of urokinase type plasminogen activator ( uPA ) to its receptor ( uPAR ) on cell surfaces has the potential to influence degradation of extracellular matrix ( ECM ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It was recently found that urokinase type plasminogen activator ( uPA ) is involved in the cleavage of its receptor ( uPAR ) on cultured cells , thereby releasing one of the receptor ' s 3 domains ( the ligand binding domain 1 ) and leaving the 2 others [ uPAR ( 2 + 3 ) ] anchored to the cell surface . ^^^ The amount of uPAR ( 2 + 3 ) may therefore be directly related to the activity of the uPA system and it is possible that the level of uPAR ( 2 + 3 ) in cancer tissue may prove to be a stronger prognostic parameter than the levels of either full length uPAR or UPA . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We conclude that pro uPA is protected against degradation via alpha 2MR / LRP when bound to uPAR due to shielding of a binding contact in the A chain , whereas the affinity of uPAR bound uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The activity of uPA on the cell surface appears to be a function of the number of uPA specific receptors ( uPAR ) and the extent of inhibition of uPA by plasminogen activator inhibitors ( PAI ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
TGF beta 1 appeared to increase uPA transcript in the 253J line in a dose dependent manner while decreasing transcript levels in the 647V line . uPAr mRNA in 253J cells increased over a 19 fold range in response to TGF beta 1 while this same transcript was decreased 14 fold in 647V cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Receptors for urokinase type plasminogen activator ( uPAR ) are present on the surface of many cell types and appear to be the key determinant controlling extracellular proteolysis catalyzed by the urokinase type plasminogen activator ( uPA ) . ^^^ Biochemical evidence has recently indicated that also uPAR is internalized with the uPA / uPAI complex . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
After binding to its receptor ( uPAR ) , active cell surface urokinase ( uPA ) is not internalized while the complex formed by uPA with plasminogen activator inhibitor type 1 ( PAI 1 ) is internalized and degraded . ^^^ To analyze the generality of this mechanism , we studied the internalization of uPA by recombinant protease nexin 1 ( rPN 1 ) , an inhibitor of thrombin , uPA , and plasmin . 125I uPA . rPN 1 complexes bound specifically to uPAR ; internalization occurred efficiently , and its time course was essentially the same as for uPA . ^^^ Internalization required binding to uPAR since it could be blocked by the anti uPAR monoclonal antibodies , by the uPAR antagonist amino terminal fragment of uPA , and by the removal of uPAR by the treatment of cells with phosphatidylinositol specific phospholipase C . ^^^ PAI 1 but unlike free uPA , bound specifically to both uPAR and alpha 2 MR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
First , the uPAR mediated increase in ANS fluorescence can be titrated by uPA as well as by its receptor binding derivatives ( the amino terminal fragment and the growth factor like module ) . ^^^ Second , an anti uPAR monoclonal antibody , capable of preventing uPA binding , can also titrate the uPAR dependent ANS fluorescence whereas other antibodies not interfering with uPA binding are unable to exert this effect . ^^^ Third , the dissociation profile of uPA uPAR complexes as a function of increasing concentrations of guanidine hydrochloride closely parallels the loss of the ANS binding site in uPAR . ^^^ Finally , liberation of the NH 2 terminal domain from uPAR by limited chymotrypsin cleavage after Tyr 87 leads to a loss of both enhanced ANS fluorescence and high affinity uPA binding . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Mononuclear phagocytes concentrate urokinase type plasminogen activator ( uPA ) at the cell surface by expressing membrane uPA receptors ( uPAR ) . ^^^ This study examines the ability of exogenous cytokines to alter expression of membrane associated uPA and uPAR in U 937 mononuclear phagocytes . ^^^ Cells were stimulated with recombinant interferon gamma ( IFN gamma ) or tumor necrosis factor alpha ( TNF alpha ) , followed by immunolabeling for uPA or uPAR and flow cytometry . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have studied the prognostic value of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and type 1 plasminogen activator inhibitor ( PAI 1 ) in tumor extracts from 84 patients with squamous cell lung carcinoma and 38 patients with large cell lung carcinoma , measuring each molecule with sandwich enzyme linked immunosorbent assays . ^^^ High uPAR levels were significantly associated with short overall survival in patients with squamous cell lung carcinomas when the median value was used as a cutoff point ( P = 0 . 038 ) , while no statistically significant prognostic impact of uPA and PAI 1 levels was found in this group of patients . ^^^ There was a positive correlation between uPAR and PAI 1 levels in both groups and between uPA and uPAR levels in the large cell carcinoma patients . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Concomitant expression of urokinase type plasminogen activator ( uPA ) and its surface receptor ( uPAR ) has been shown to correlate strongly with a more invasive tumor cell phenotype . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Mononuclear phagocytes ( Mphi ) produce urokinase type plasminogen activator ( uPA ) and also express a specific cell surface receptor for urokinase , uPAR . ^^^ Inactivating the catalytic activity of uPAR bound uPA had no effect on chemotaxis . ^^^ Similarly , blocking uPAR expression with an antisense oligonucleotide to uPAR completely ablates chemotaxis , but blocking uPA expression with an antisense oligonucleotide to uPA has a minimal effect . ^^^ We therefore demonstrate that expression and unimpeded function of uPAR plays an obligate role in M phi chemotaxis by mechanisms that are largely independent of its ligand , uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we demonstrate that a highly metastatic melanoma cell line ( M24met ) that secretes uPA expresses high levels of the uPA receptor ( uPAR ) , 2 . 4 10 10 ( 6 ) binding sites / cell with a KD of 5 . 67 10 10 ( 10 ) M . ^^^ This contention is based on the finding that an antibody against uPAR ( monoclonal antibody 3936 ) inhibited invasion of M24met cells through a reconstituted basement membrane ( Matrigel ) up to 33 % , while a reduction of uPA catalytic activity by its plasminogen activator inhibitor 2 resulted in 46 % inhibition of invasion . ^^^ Furthermore , uPAR is involved in signal transduction events in M24met cells , since both uPA and its amino terminal fragment stimulated the migration of melanoma cells toward Matrigel , resulting in maximal increases of 32 and 72 % , respectively . ^^^ Our results indicate that both uPA and uPAR are involved in melanoma metastasis and that uPAR contributes to at least two important steps in this process , matrix dissolution and migration . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
As determined by histopathological methods , the malignant tumors showed statistically significantly higher expression of urokinase plasminogen activator ( uPA ) , type 1 plasminogen activator inhibitor ( PAI 1 ) , and especially urokinase plasminogen activator receptor ( uPAR ) than benign tissues . ^^^ When the tumors express high amounts of uPA , they express a high amount of uPAR in 50 % of cases and PAI 1 in 57 . 3 % of cases . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have identified a soluble form of the human urokinase plasminogen activator ( uPA ) receptor ( uPAR ) in the ascitic fluids from patients with ovarian cancer . ^^^ After purification of uPAR from the ascitic fluids by ligand affinity chromatography ( pro uPA Sepharose ) , the uPAR was initially identified by cross linking to a radiolabeled amino terminal fragment of human uPA . ^^^ The uPAR purified from the ascitic fluid has no bound ligand ( uPA ) , as similar amounts can be purified by ligand affinity chromatography as by immuno affinity chromatography . uPAR from ascitic fluids partitions in the water phase after a temperature dependent phase separation of a detergent extract . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cellular receptor for urokinase type plasminogen activator ( uPAR ) binds pro urokinase ( pro uPA ) and facilitates its conversion to enzymatically active urokinase ( uPA ) . uPA in turn activates surface bound plasminogen to plasmin , a process of presumed importance for a number of biologic processes including cell migration and resolution of thrombi . ^^^ Stimulation of neutrophils with FMLP results in translocation of uPAR as well as of pro uPA from the secretory vesicles , whereas stimulation with PMA is required to translocate material from specific granules . ^^^ Flow cytometry of neutrophils saturated with exogenous diisopropyl fluorophosphate uPA shows a large excess ( approximately 90 % ) of unoccupied uPAR on resting as well as FMLP and PMA stimulated neutrophils , suggesting a possible role for exogenous pro uPA in providing neutrophils with a potential for plasminogen activation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These studies provide the tools for examining uPAR function in fibrinolysis , tumor invasion and metastasis in the rat and for identifying the mechanism of species specificity in uPA actions . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of the urokinase plasminogen activator ( uPA ) to a specific cell surface receptor ( uPAR ) plays a crucial role in proteolysis during tissue remodelling and cancer invasion . ^^^ In a variant of the assay , the occupied fraction of uPAR is selectively detected with a uPA antibody . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To study the role of the uPA receptor ( uPAR ) in such interactions , a human osteosarcoma cell line ( HOS ) , which normally expresses low levels of uPAR , was transfected with human uPAR complementary DNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We propose that the alternatively spliced uPAR mRNA encodes a soluble uPA binding protein , the possible function of which is discussed . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We studied the distribution of the uPA receptor ( uPAR ) on human fibroblasts ( HES ) and rhabdomyosarcoma ( RD ) cells by immunofluorescence and immunoelectron microscopy . ^^^ In contrast , uPAR R 4 and uPA antibodies at the focal contact sites remained mostly within focal contacts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Northern blot analysis confirmed that glioblastoma cells like other human cell lines express a 1 . 4 kilobase uPAR mRNA and 2 . 4 kilobase uPA mRNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of this study was to investigate by flow cytometry the expression of the UPA R ( Urokinase type plasminogen activator receptor CD 87 ) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The study was extended to urokinase ( uPA ) secretion and surface expression of its receptor ( uPAR ) . ^^^ As uPA and uPAR were differently affected , it is suggested that an increase in cytosolic calcium leads to a reduced pericellular proteolysis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( CD 87 ) : a new target in tumor invasion and metastasis . ^^^ The strong correlation between elevated uPA and / or PAI 1 values in primary cancer tissues and the malignant phenotype of cancer cells has prompted to explore new tumor biology oriented concepts in order to suppress uPA or uPA receptor ( CD 87 ) expression or to abrogate interaction of uPA with CD 87 . ^^^ Various very different approaches to interfere with the expression or reactivity of uPA or CD 87 at the gene or protein level were successfully tested including antisense oligonucleotides , antibodies , inhibitors and recombinant or synthetic uPA and CD 87 analogues . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) converts plasminogen to plasmin which degrades various extracellular matrix components . uPA is focused to the cell surface via binding to a specific receptor ( uPAR , also termed CD 87 ) . uPAR bound uPA mediates pericellular proteolysis in a variety of biological processes , e . g . cell migration , tissue remodeling and tumor invasion . ^^^ We have developed a competitive microtiter plate based chromogenic assay which allows the analysis of uPA / uPAR interaction . ^^^ Proteolytically active uPA ( HMW uPA ) is added to the microtiter plate attached uPAR . ^^^ Substances interfering with binding of HMW uPA to uPAR diminish the generation of plasmin , as indicated by a reduction of cleaved chromogenic substrate . ^^^ This assay was used to analyze the inhibitory capacity of a variety of proteins and peptides , respectively , on the uPA / uPAR interaction : 1 ) uPAR and uPAR variants expressed in CHO cells , yeast or E . coli , 2 ) the aminoterminal fragment ( ATF ) of human uPA or yeast recombinant pro uPA , 3 ) synthetic peptides derived from the sequence of the uPAR binding region of uPA , and 4 ) antibodies directed against uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Within 5 days , smooth muscle cells ( SMCs ) on the luminal surface expressed the mRNA for tissue type plasminogen activator ( TPA ) , urokinase type plasminogen ( UPA ) , the receptor for UPA ( UPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Quiescent endothelial cells did not express TPA , UPA , UPAR , or PAI 1 mRNA . ^^^ UPA , and UPAR , as well as PAI 1 . ^^^ UPA and UPAR expression was highly restricted to cells at the wound edge and was not present elsewhere . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we characterize the expression of tissue type ( tPA ) and urokinase ( uPA ) PAs , as well as the urokinase cell surface receptor ( uPAR ) during differentiation of cultured cells from mouse dorsal root ganglia . ^^^ Interestingly , in situ hybridization studies of the cultures show that tPA mRNA is restricted to small sensory neurons , whereas uPA mRNA is localized predominantly in large sensory neurons . uPAR mRNA is expressed by both neuronal subpopulations and , to a lesser extent , by Schwann cells and fibroblasts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Physiological concentrations of urokinase plasminogen activator ( uPA ) stimulated a chemotactic response in human monocytic THP 1 through binding to the urokinase receptor ( uPAR ) . ^^^ Our data show that uPA induced signal transduction takes place via uPAR , involves activation of intracellular tyrosine kinase ( s ) and requires an as yet undefined adaptor capable of connecting the extracellular ligand binding uPAR to intracellular transducer ( s ) . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It was found that urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and plasminogen activator inhibitor type 1 ( PAI 1 ) were expressed diffusely in most thyroid carcinomas . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cellular distribution of mRNAS for urokinase type plasminogen activator ( uPA ) , its specific receptor ( uPAR ) , and its inhibitors ( PAI 1 and 2 ) in mouse skin was analyzed by in situ hybridization after topical application of the tumor promoter phorbol 12 myristate 13 acetate . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To determine if the effects of uPAR are mediated through its ligand , monocytes were pre treated with AS oligo to block uPA expression . ^^^ Unlike the effects of blocking uPAR expression , AS uPA oligo increased adhesion by 46 % ( P < 0 . 005 ) , and exogenous intact uPA , but not uPA fragments , reversed this effect . ^^^ This function of uPAR is not dependent upon its occupancy with uPA , which negatively influences adhesion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : The immunohistochemical localization of uPAR , uPA , tPA ) and PAI 1 was evaluated by using the avidin biotin immunoperoxidase technique and affinity purified monoclonal antibodies from American Diagnostica Inc . ^^^ CONCLUSIONS : We showed that overexpression of uPAR , uPA , and its main inhibitor , PAI 1 , is a constant feature of invasive ductal breast carcinomas . ^^^ The combined increased expression of uPA and its cellular receptor , uPAR on the surface of tumor epithelial cells may account for the activation of the proteolytic system which occurs in breast cancer . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The amino terminal fragment of human uPA ( ATF ; amino acids 1 135 ) , which contains the binding site for the uPA receptor ( uPAR , CD 87 ) was expressed in the yeast Saccharomyces cerevisiae . ^^^ Recombinant yeast ATF , modified and extended by an amino terminal in frame insertion of a His 6 tract , was purified from total protein extracts by nickel chelate affinity chromatography and shown to be functionally active since it efficiently competes with uPA for binding to cell surface associated uPAR . ^^^ All mutant ATF proteins but one ( deletion of Ser 26 ) were expressed in a stable form ( about 20 30 ng / mg total protein ) and the binding capacity of each mutant was tested by a uPA ligand binding assay employing recombinant uPAR immobilized to a microtiter plate . ^^^ In a different set of experiments , those amino acids of the uPAR binding region of uPA that are only conserved between man and baboon but not in other species were altered : whereas substitution of Thr 18 by alanine or Asn 32 by serine had hardly any effect , replacement of Asn 22 by tyrosine and Trp 30 by arginine ( both positions are strictly conserved in other mammals ) led to ATF variants incapable of interacting with human uPAR . ^^^ The results presented for the ATF mutants and uPA derived peptides may provide clues necessary to establish the nature of the physical interaction of uPA with its receptor and may help to develop uPA derived peptide analogues as potential therapeutic agents to block tumor cell associated uPA / uPAR interaction . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The availability of gene targeted mice deficient in the urokinase type plasminogen activator ( uPA ) , urokinase receptor ( uPAR ) , tissue type plasminogen activator ( tPA ) , and plasminogen permits a critical , genetic based analysis of the physiological and pathological roles of the two mammalian plasminogen activators . ^^^ However , uPAR / / tPA / mice do not develop the pervasive , multi organ fibrin deposits , severe tissue damage , reduced fertility , and high morbidity and mortality observed in mice with a combined deficiency in tPA and the uPAR ligand , uPA . ^^^ Furthermore , uPAR / / tPA / mice do not exhibit the profound impairment in wound repair seen in uPA / / tPA / mice when they are challenged with a full thickness skin incision . ^^^ These results indicate that plasminogen activation focused at the cell surface by uPAR is important in fibrin surveillance in the liver , but that uPA supplies sufficient fibrinolytic potential to clear fibrin deposits from most tissues and support wound healing without the benefit of either uPAR or tPA . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously shown that the overall efficiency of this plasminogen activation system is greatly enhanced by its assembly on the cell surface , involving binding of pro uPA to its cellular binding site uPAR , and the concurrent cellular binding of plasminogen . ^^^ In contrast to the increased efficiencies of plasminogen activation and pro uPA activation observed with cell surface uPAR , soluble uPAR had an inhibitory effect on both of these individual reactions . ^^^ Soluble uPAR also caused no increase in the low , but discernible , intrinsic activity of pro uPA . ^^^ These observations confirm the previous interpretation of the observations made with cell surface uPAR that the mechanism of the enhanced plasmin generation is due to the catalytically favorable interaction of uPAR bound uPA / pro uPA with cell bound plasminogen / plasmin , rather than direct effects on the properties of uPA or pro uPA on binding to uPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using monoclonal antibodies against uPA and its receptor uPAR , we have investigated the contribution of uPA and uPAR to invasive capacity in an in vitro invasion assay . ^^^ MDA MB 231 BAG cells were found to express high protein levels of uPA , uPAR and PAI 1 . ^^^ MDA MB 435 BAG cells produced low amounts of uPA , PAI 1 and moderate amounts of uPAR , whereas MCF 7 BAG cells showed low levels of uPA , uPAR and PAI 1 protein . ^^^ In a plasmin generation assay MDA MB 231 BAG cells were highly active in mediating plasmin formation , which could be abolished by adding either an anticatalytic monoclonal antibody to uPA ( clone 5 ) or an anti uPAR monoclonal antibody ( clone R 3 ) , which blocks binding of uPA to uPAR . ^^^ Testing MDA MB 231 BAG cells in the Matrigel invasion assay revealed that invasion could be inhibited in a dose dependent manner either by the clone 5 uPA antibody or by the clone R 3 uPAR antibody , suggesting that the cell surface uPA system is actively involved in this invasive process . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator ( uPA ) to a specific receptor ( uPAR ) on human lung fibroblasts enables it to regulate cellular proteolysis and remodeling of the extracellular matrix . ^^^ Ribonuclease ( RNase ) protection assays showed higher levels of uPAR messenger ribonuleic acid ( mRNA ) in each of the five fibrotic cell lines than in normal fibroblasts . uPA was mitogenic for normal as well as fibrotic fibroblasts , indicating that receptor binding concurrently localizes cellular proteolytic activity and stimulates mitogenesis . ^^^ Morphometry and immunohistochemical analysis showed that uPAR , as well as uPA , was increased in fibroblasts in fibrotic lung tissue . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this paper , we demonstrated the presence of uPA in the conditioned medium , and of uPA receptor ( uPAR ) on the cell surface of 8701 BC cells , which therefore have the potential for an autocrine mechanism of uPA mediated stimulation . ^^^ We examined whether exogenous addition of either intact uPA , or its amino terminal fragment ( uPA ATF ) , which lacks catalytic activity but retains the uPAR binding site and a growth factor like domain , or immunoneutralisation of endogenous uPA uPAR interactions could exert any effect on the proliferative and invasive behaviour of 8701 BC cells . ^^^ The data demonstrate that , while uPA promotes growth and invasion of 8701 BC cells , its effect reversed by blocking uPA uPAR interactions , uPA ATF not only fails to impart growth factor like signals , but also restrains cell invasion in vitro . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator ( uPA ) to its glycosylphosphatidylinositol anchored receptor ( uPAR ) initiates signal transduction , adhesion , and migration in certain cell types . ^^^ To determine whether some of these activities may be mediated by associations between the uPA / uPAR complex and other cell surface proteins , we studied the binding of complexes composed of recombinant , soluble uPA receptor ( suPAR ) and single chain uPA ( scuPA ) to a cell line ( LM TK fibroblasts ) that does not express glycosylphosphatidylinositol ( GPI ) anchored proteins to eliminate potential competition by endogenous uPA receptors . scuPA induced the binding of suPAR to LM TK cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasminogen and plasmin system , which is mainly regulated by urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitor ( PAI 1 ) , is generally believed to play a role in cancer invasion and metastasis . ^^^ This study was conducted to investigate the role of uPA , uPAR and PAI 1 in the invasion and metastasis of gastric adenocarcinoma . ^^^ The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR , and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Recent studies show that uPAR itself is a high affinity adhesion receptor for vitronectin and that urokinase ( uPA ) is an activator of this adhesive function . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Our results therefore demonstrate the role of uPAR in tumor progression , due to its ability to localize uPA within the tumor cell milieu . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
RESULTS : Concentrations of all antigens ( uPA , tissue type PA ( tPA ) , uPAR , and PAI 1 ) , were significantly greater in RA than OA ; those in OA were significantly greater than normal . ^^^ Antigen concentrations ( uPA , tPA , and uPAR ) in NGOA differed from those in other subclasses of OA , but the species of PA present did not appear to vary between disease groups . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) is a multifunctional protein involved in both extracellular proteolysis and signal transduction . uPA usually mediates its actions while attached to a membrane bound receptor , termed uPAR . ^^^ At both levels , concentrations of uPA were significantly correlated with those for uPAR . uPA levels also correlated significantly with cathepsin B and cathepsin D but not with cathepsin L , MMP 8 or MMP 9 levels . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasminogen activator ( PA ) / plasmin system has been extensively investigated in these processes , and descriptive studies have demonstrated that urokinase type PA ( uPA ) , uPA receptor ( uPAR ) and PA inhibitor 1 ( PAI 1 ) are expressed by endothelial cells during angiogenesis in vivo . ^^^ These findings are discussed in the context of recent observations on uPA , uPAR , PAI 1 and plaminogen deficient mice , in which developmental and physiological angiogenesis appear to occur normally . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Embryo implantation in mouse : fetomaternal coordination in the pattern of expression of uPA , uPAR , PAI 1 and alpha 2MR / LRP genes . ^^^ The sites of synthesis of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and alpha 2 macroglobulin receptor / low density lipoprotein receptor related protein ( alpha 2MR / LRP ) transcripts were determined by in situ hybridization . ^^^ Starting from day 6 . 5 , endothelial cells of newly forming vessels also transcribed uPA gene . uPAR and alpha 2MR / LRP were in all stages expressed by decidual tissue , and their expression domains overlapped in large areas . ^^^ Immunohistochemistry with uPA and PAI 1 antibodies revealed areas of co localization of these secreted proteins with the expression domains of uPAR and alpha 2MR / LRP , which is of great interest in view of the role of these two receptors in clearing uPA PAI 1 complexes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Pro uPA as well as uPA binds to the cellular uPA receptor ( uPAR ) which has a central function in cell dependent acceleration of the cascade system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Secreted pro uPA can immediately bind to the specific uPA receptors ( uPAR ) on tumor cell surface with high affinity . ^^^ The uPAR specifically recognizes enzymatically inactive pro uPA and active high molecular weight uPA ( HMW uPA ) by their growth factor like terminal domain . uPAR is a glycoprotein of approximately 55 kDa ; the affinity for uPA is high ( 0 . 2 nM ) and the rate of dissociation is low . ^^^ In some cell types uPAR localizes uPA to cell cell and cell substratum contact sites , providing the possibility of a directional proteolysis that may be involved in cell migration and invasion . ^^^ Recently it has been reported that competitive displacement of uPA from uPAR resulted in decreased proteolysis , suggesting that the cell surface is the preferred site for uPA mediated protein degradation . ^^^ Various very different approaches to interfere with the expression or reactivity of uPA or uPAR at the gene or protein level were successfully tested including antisense oligonucleotides , antibodies , inhibitors and recombinant or synthetic uPA and uPAR analogues . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The clinical significance of secreted levels of uPA , its receptor ( uPAR ) , and its inhibitors ( PAI 1 and PAI 2 ) in the ascites of patients with epithelial ovarian cancer patients was investigated . ^^^ METHODS : uPA , uPAR , PAI 1 , and PAI 2 were measured in the primary ascites of 36 patients with epithelial ovarian cancer by enzyme linked immunosorbent assay , and normalized to protein content . ^^^ However , the ratio of uPAR normalized for uPA content correlated inversely with FIGO stage and residual disease , with a significant association between high uPAR / uPA level and prolonged survival and DFI . ^^^ CONCLUSION : Secreted uPAR / uPA appears to measure tumor burden and predicts prolonged DFI and survival , but was not found to be an independent prognostic factor on multivariate analysis . ^^^ Therefore , secreted uPAR and PAI 1 may modulate uPA activity and lead to improved outcome . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Induction of the urokinase type plasminogen activator receptor ( uPAR ) promotes cell adhesion through its interaction with vitronectin ( VN ) in the extracellular matrix , and facilitates cell migration and invasion by localizing uPA to the cell surface . ^^^ Taken together , these results suggest a dynamic regulatory role for PAI 1 and uPA in uPAR mediated cell adhesion and release . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition , the different uPA ELISA kits use antibodies which differ in specificity and affinity for the various forms of uPA including pro uPA , HMW uPA , LMW uPA , the aminoterminal fragment ( ATF ) and complexes with inhibitors ( PAI 1 and PAI 2 ) and the receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) , when bound to its cell surface receptor ( uPAR ) , is an active cell surface protease . uPAR expression has been associated with cell activation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Keratinocytes synthesize urokinase type plasminogen activator ( uPA ) and a specific cell surface receptor for uPA ( uPA R , CD 87 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Ligand blotting and purification experiments show an equivalent increase in the synthesis of a cell surface protein corresponding to the endothelial cell uPA receptor ( uPAR ) on the basis of M , ( 45 50 kDa ) and sensitivity to phosphatidylinositol specific phospholipase C ( PI PLC ) . ^^^ Thus , the increase in uPA binding capacity of endothelial cells is mediated by an increased expression of uPAR . ^^^ Therefore , it appears to be distinct from the bFGF / uPA inducing factor secreted by the same cells , and from other heparin binding cytokines that upregulate uPAR expression in endothelial cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase plasminogen activator ( uPA ) interacts with its cell surface receptor ( uPAR ) , providing an inducible , localized cell surface proteolytic activity , thereby promoting cellular invasion . ^^^ Evidence is provided for a novel function of cell surface associated uPA . uPAR . ^^^ Specifically , induction of cell surface expression of uPA . uPAR by growth factors or phorbol ester was necessary for vitronectin dependent carcinoma cell migration , an event mediated by integrin alphavbeta 5 . ^^^ Cell migration on vitronectin was blocked with either a soluble form of uPAR , an antibody that disrupts uPA binding to uPAR , or a monoclonal antibody to alphavbeta 5 . ^^^ Moreover , plasminogen activator inhibitor type 2 blocked this migration event but did not affect adhesion , suggesting a direct role for uPA enzyme activity in this process and that migration but not adhesion of these cells is regulated by uPA . uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Targeting of proteolytic activity may occur via focalized expression of uPA and its cell surface receptors ( uPAR ) . ^^^ The cell surface binding of uPA via its growth factor like domain to uPAR localizes and activates the protease , but may also initiate transmembrane signalling of biological responses , including migration / invasion and proliferation . ^^^ As the uPAR lacks intracellular signalling domains , the signals may be transduced via interactions between uPA / uPAR and more classical signalling receptors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Dispase mediated basal detachment of cultured keratinocytes induces urokinase type plasminogen activator ( uPA ) and its receptor ( uPA R , CD 87 ) . ^^^ Keratinocytes synthesize and secrete urokinase type plasminogen activator ( uPA ) , which is bound in an autocrine manner to a specific receptor ( uPA R , CD 87 ) at their surface . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To clarify the specific expression and regulation of mRNAs for urokinase ( uPA ) , its receptor ( uPAR ) , and type 1 plasminogen activator inhibitor ( PAI 1 ) , 1 analyzed RNA from four human cancer cell lines by RNA blotting after treatment with cycloheximide , anisomycin , emetine or puromycin . ^^^ Different time patterns of induction for uPA , uPAR and PAI 1 mRNA suggest that even in the same cell type , inhibitors of protein synthesis mediate their effects on various genes through different mechanisms . ^^^ Thus , induction of uPA , uPAR , and PAI 1 transcripts by inhibitors of protein synthesis was dependent on the gene , the cell line , and the type of inhibitor , and inhibition of protein synthesis per se was not sufficient for induction of these transcripts . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The levels of uPA , its inhibitors PAI 1 and PAI 2 , and the uPA receptor ( uPAR ) have prognostic value in breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urinary type plasminogen activator , urokinase ( uPA ) is localized on the cell surface through the binding of a specific receptor , the uPA receptor ( uPAR ) . ^^^ The comparison of uPAR expression between these cell lines and peripheral blood cells and it correlation with plasminogen receptors , tPA receptors and LRP expression offers new insights regarding potential mechanisms for regulation of uPA uPAR mediated pericellular proteolysis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It binds to a specific membrane receptor denominated uPA receptor ( uPAR ) . uPA activates plasminogen to form plasmin , which participates in tissue degradation and proteolysis . ^^^ Binding of uPA to its receptor accelerates UPA ' s own activation from pro uPA , enhancing the activity of the uPA / uPAR cascade . ^^^ Using immunohistochemistry and Northern blot analysis , we analysed the role of uPA and uPAR in 30 human pancreatic cancers . ^^^ In addition , in desmoplastic areas adjacent to the cancer cells , moderate uPA and uPAR immunoreactivity was detectable . ^^^ Northern blot analysis revealed a sixfold and a fourfold increase in uPA and uPAR mRNA levels in pancreatic cancer , respectively , in comparison with normal controls ( P < 0 . 01 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) binds to a specific cell surface receptor , uPAR . ^^^ The formation of uPAR ( 2+3 ) on cultured U 937 cells is either directly or indirectly mediated by uPA itself . ^^^ In a soluble system , uPA can cleave purified uPAR , but the low efficiency of this reaction has raised doubts as to whether uPA is directly responsible for uPAR cleavage on the cells . ^^^ We now report that uPA catalyzed cleavage of uPAR on the cell surface is strongly favored relative to the reaction in solution . ^^^ The time course of uPA catalyzed cleavage of cell bound uPAR was studied using U 937 cells stimulated with phorbol 12 myristate 13 acetate . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Epitope mapped monoclonal antibodies as tools for functional and morphological analyses of the human urokinase receptor in tumor tissue . uPAR ( CD 87 ) , the receptor for the urokinase type plasminogen activator ( uPA ) facilitates tumor cell invasion and metastasis by focusing uPA proteolytic activity to the cell surface . ^^^ All MAbs reacted under reducing conditions in immunoblot analyses with E . coli expressed uPA and also with highly glycosylated , functionally intact , recombinant human uPAR expressed in Chinese hamster ovary ( CHO ) cells . ^^^ Saturation of uPAR with uPA on U 937 cells completely blocked interaction of MAb IIIF 10 with uPAR ( mapped epitope , amino acids 52 to 60 of domain 1 of uPAR ) . ^^^ In turn , preincubation of U 937 cells with MAb IIIF 10 efficiently reduced binding of uPA to uPAR , indicating that the epitope detected by MAb IIIF 10 is located within or closely to the uPA binding site of uPAR , and thus , this site may be a target to influence uPA / uPAR mediated proteolysis in tumors . ^^^ Binding of MAbs IID 7 or IIIB 11 ( mapped epitope , amino acids 125 to 132 of domain 2 of uPAR ) to uPAR is not affected when uPAR is occupied by uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we study the influence of the protease urokinasetype plasminogen activator ( uPA ) and its receptor ( uPAR ) on melanoma cell adhesion to , and migration on , the extracellular matrix protein vitronectin ( VN ) . ^^^ Soluble uPAR can inhibit this effect , indicating that uPA / uPAR on melanoma cells can function as a VN receptor . ^^^ In the absence of bivalent cations , uPA / uPAR can promote cell attachment on VN , but not cell spreading , suggesting that the glycosylphosphatidylinositol ( GPI ) anchored uPAR alone is unable to organize the cytoskeleton . ^^^ Chemotactic melanoma cell migration on a uniform VN matrix is inhibited by uPA and ATF , implying that cell motility decreases when uPA / uPAR acts as a VN receptor . ^^^ In contrast , plasminogen activator inhibitor 1 ( PAI 1 ) can stimulate melanoma cell migration on VN , presumably by inhibiting uPA / uPAR mediated cell adhesion to VN and thereby releasing the inhibition of cell migration induced by uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The high level of soluble uPAR in PNH plasma competed with the membrane uPAR expressed by normal blood neutrophils for binding to urokinase type plasminogen activator ( uPA ) . ^^^ We also found that uPA complexed with soluble uPAR was partly resistant to inactivation by plasminogen activator inhibitors in the plasma , although uPA was inactivated similarly by plasma containing high and low levels of uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Migrating , undifferentiated myoblasts express urokinase plasminogen activator ( uPA ) and its cell surface receptor ( uPAR ) . ^^^ When myoblasts reach confluence , cease migrating , and start to differentiate , uPAR gets downregulated , and uPA becomes redistributed from the cell surface to the extracellular space . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The different components of this system . e . g . urokinase plasminogen activator ( uPA ) , its receptor uPAR , as well as its main inhibitor plasminogen activator inhibitor type 1 ( PAI 1 ) have all been shown to have prognostic value in breast cancer , i . e . high tumor levels are associated with a poor prognosis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
However , unlike the sample lectin carbohydrate interaction that appears to govern the association between Mo 1 and Fc gamma RIIIB , effective Mo 1 dependent uPAR signaling also depends on the binding of intact uPA to uPAR ( the receptor binding ATF of uPA proving insufficient to prime neutrophils for an enhanced burst response to FMLP ) . ^^^ In support of this model is the fact that exposure of neutrophils to ATF reduced the degree of molecular proximity between Mo 1 and uPAR ( the latter probably occupied by endogenous intact uPA ) and increased the molecular association between Mo 1 and Fc gamma RIIIB ( both as detected by quantitative RET ) . ^^^ Whereas the contribution of intact uPA to the interaction between Mo 1 and uPAR remains speculative ( based on the indirect data available ) , no such ambiguity exists for the role of the LPS / LBP ligand in regulating the association between Mo 1 and CD 14 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Considerable evidence links urokinase plasminogen activator ( uPA ) bound to its surface receptor ( uPAR ) with enhanced invasiveness of cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of the uPA receptor ( uPAR ) to pro uPA / uPA might affect separate steps of the reciprocal activation reaction , or it might induce a significant pro uPA activity . ^^^ To distinguish between these possibilities the effect of a recombinant soluble ( residues 1 277 ) form of uPAR , uPAR ( 1 277 ) peptide , on reciprocal pro uPA / plasminogen activation was studied . uPAR ( 1 277 ) peptide attenuated reciprocal zymogen activation , and the results suggested that this was due to a decreased accessibility of the pro uPA / uPAR ( 1 277 ) peptide complex to activation by plasmin . ^^^ Kinetic analysis of separate activation steps revealed that this was due to a threefold stimulation of plasminogen activation by uPA / uPAR ( 1 277 ) peptide combined with a sixfold stimulation of plasmin ' s activation of pro uPA / uPAR ( 1 277 ) peptide . ^^^ The results suggested that poly ( D lysine ) provided a template for a catalytically favourable interaction between plasminogen / plasmin and the uPAR ( 1 277 ) peptide complex with pro uPA / uPA . ^^^ There was no indication of a significant uPAR ( 1 277 ) peptide induced enhancement of pro uPA activity . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Low density lipoprotein receptor related protein ( LRP ) mediates the endocytosis of diverse ligands , including urokinase plasminogen activator ( uPA ) and its receptor , uPAR , which have been implicated in cellular migration . ^^^ The difference in migration velocity was duplicated in culture wells that were precoated with serum or vitronectin and partially duplicated in wells coated with fibronectin but not in wells coated with type 1 collagen or Matrigel . uPA was detected in MEF 2 conditioned medium ( CM ) at a concentration of 0 . 30 + / 0 . 02 nM , which was 13 fold higher than the level detected in MEF 1 CM or PEA 10 CM , suggesting one potential mechanism for the enhanced migration of MEF 2 cells . uPAR was also increased on MEF 2 cells by 4 5 fold , as determined by PI PLC release , and by 2 . 5 fold , as determined by a uPA / uPAR activity assay . ^^^ These studies demonstrate alterations in cellular migration and in the activity of the uPA / uPAR system which accompany complete deficiency of LRP expression in fibroblasts . ^^^ We propose that uPA and uPAR form an autocrine loop for promoting fibroblast migration and that LRP counteracts the activity of this system . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Evidence of a non conventional role for the urokinase tripartite complex ( uPAR / uPA / PAI 1 ) in myogenic cell fusion . ^^^ Myogenic cell fusion was associated with increased cell associated urokinase type plasminogen activator ( uPA ) activity , cell associated uPAR , and uPAR occupancy . ^^^ Decreased fusion rates induced by interfering with uPAR / uPA / PAI 1 interactions were not associated with significant changes in mRNA levels of both the myogenic regulatory factor myogenin and its inhibitor of DNA binding , Id . ^^^ We conclude that muscle cell fusion largely depends on interactions between the members of the urokinase complex ( uPAR / uPA / PAI 1 ) , but does not require proteolytic activation of plasmin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These data indicate that PAI 1 plays a direct role in dynamic cell adhesion particularly at the leading edge , where increased levels of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) are localized in migrating cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Levels of uPA , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) were measured semiquantitatively in paraffin sections of tumours from 147 patients with NSCLC . ^^^ There was a significant positive relationship between PAI 1 levels and T stage ( p = < 0 . 05 ) in the total group , and survival status ( p = < 0 . 05 ) in the SCC subgroup alone . uPA and uPAR levels were not significantly associated with tumour staging or survival . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The GPI anchored urokinase plasminogen activator receptor ( uPAR ) does not internalize free urokinase ( uPA ) but readily internalizes and degrades uPA : serpin complexes in a process that requires the alpha 2 macroglobulin receptor / low density lipoprotein receptor related protein ( alpha2MR LRP ) . ^^^ In this paper we show that during internalization of uPA : serpins at 37 degrees C , analysed by FACScan , immunofluorescence and immunoelectron microscopy , an initial decrease of cell surface uPAR was observed , followed by its reappearance at later times . ^^^ Recycling was directly demonstrated in cell surface biotinylated , uPA : PAI 1 exposed cells in which biotinylated uPAR was first internalized and subsequently recycled back to the surface upon incubation at 37 degrees C . ^^^ In fact , uPAR was resistant to PI PLC after the 4 degrees C binding of uPA : PAI 1 to biotinylated cells , but upon incubation at 37 degrees C PI PLC sensitive biotinylated uPAR reappeared at the cell surface . ^^^ Binding of uPA : PAI 1 by uPAR , while essential to initiate the whole process , was , however , dispensable at later stages as both internalization and recycling of uPAR could be observed also after dissociation of the bound ligand from the cell surface . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Numerous studies have demonstrated the importance of urokinase plasminogen activator ( uPA ) and its receptor , uPAR , in the processes of tumor progression and metastasis . ^^^ Thus , the uPA / uPAR interaction may represent an important target for inhibiting metastatic disease . ^^^ BIAcore analysis and competition binding assays using LOX human malignant melanoma cells expressing uPAR indicated that the purified recombinant protein possessed similar ligand binding characteristics to that of human uPA . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Evidence has accumulated that urokinase type plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) and receptor ( uPAR ) are involved in tumor invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Strong clinical and experimental evidence has accumulated that the tumor associated serine protease plasmin , its activator uPA ( urokinase type plasminogen activator ) , the receptor uPA R ( CD 87 ) , and the inhibitors PAI 1 and PAI 2 are linked to cancer invasion and metastasis . ^^^ Various very different approaches to interfere with the expression or reactivity of uPA or CD 87 at the gene or protein level were successfully tested including antisense oligonucleotides , antibodies , enzyme inhibitors , and recombinant or synthetic uPA and uPA R analogues . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Although tissue type plasminogen activator ( tPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) are believed to be involved in the biochemical cascade leading to extracellular matrix degradation during ovulation , the presence and possible role of urokinase type PA ( uPA ) and its receptor ( uPAR ) in follicular wall remodeling during follicular development are poorly understood . ^^^ In the current studies , we have examined their presence in the rat ovary and compared the changes in both uPA and uPAR expression with those of tPA and PAI 1 during follicular growth in vivo . ^^^ Whereas uPA transcript and protein levels were highest at the earliest stage of follicular growth examined and decreased markedly before the expected time of ovulation , the opposite was true for uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Internalization of the urokinase type plasminogen activator ( uPA ) requires two receptors , the uPA receptor ( uPAR ) and the low density lipoprotein receptor related protein ( LRP ) / alpha2 macroglobulin ( alpha2M ) receptor . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Little is known about the behavior and prognostic impact of the receptor for UPA ( UPAR ) . ^^^ The aims of the present study were : ( 1 ) to measure UPAR , UPA and PAI 1 levels in GC and in non malignant tissue distant from the tumor ( NORM ) ; ( 2 ) to evaluate their relationship with histomorphological parameters ; and ( 3 ) to determine their prognostic value . ^^^ UPAR , UPA and PAI 1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery . ^^^ UPAR , UPA and PAI 1 were significantly higher in GC vs NORM , in the presence of metastasis ( UPAR , UPA ) and in undifferentiated GC ( UPAR , PAI 1 ) . ^^^ UPAR significantly correlated with UPA and PAI 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To explore whether downregulation of uPAR inhibits tumor formation and invasiveness , a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR ' s 5 ' end in an antisense orientation , resulting in a reduced number of uPA receptors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression and localization of mRNA ' s for tissue plasminogen activator ( tPA ) , urokinase PA ( uPA ) , uPA receptor ( uPAR ) and inhibin subunits , alpha , beta A and beta B in monkey testes was investigated . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A sandwich type ELISA has been developed for the assessment of complexes between urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in extracts of squamous cell lung carcinomas . ^^^ The assay is based on a combination of rabbit polyclonal anti uPA antibodies and a biotinylated mouse anti uPAR monoclonal antibody ( MAb ) . ^^^ A linear dose response is obtained with up to 40 fmol / ml of uPA : uPAR complexes , while uPA and uPAR separately do not cause any response in the ELISA . ^^^ A buffer which has been used previously for optimal extraction of uPAR yields the highest amounts of uPA : uPAR complexes . ^^^ Absorption of tumor extracts with anti uPA or anti uPAR MAbs results in a complete disappearance of the ELISA signal , demonstrating the specificity of the ELISA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The intrinsic activity of single chain pro urinary type plasminogen activator ( pro uPA ) and whether its receptor ( uPAR ) potentiates this activity remains controversial . ^^^ In this report , the pro uPA / uPAR ( 1 281 ) peptide complex in solution is shown to have equivalent plasminogen activator activity to that of active two chain uPA ( tc uPA ) . ^^^ The pro uPA / uPAR ( 1 281 ) peptide complex at 1 nM displayed similar activity to that of tc uPA for either [ Glu 1 ] plasminogen or [ Lys 77 ] plasminogen in chromogenic assays with Spl present as the plasmin substrate . ^^^ When assayed with another plasmin substrate , S 2251 , the pro uPA / uPAR ( 1 281 ) peptide complex was unable to activate plasminogen . ^^^ The pro uPA / uPAR ( 1 281 ) peptide complex and tc uPA also showed a similar extent of plasminogen activation as measured by SDS / PAGE , when incubated with plasminogen and Spl in the presence of 100 micro M aprotinin , and plasminogen activation by pro uPA alone was also stimulated in the presence of Spl in this assay . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Pretreatment of SaOS 2 cells with the protein tyrosine kinase inhibitor herbimycin and recombinant soluble uPA receptor ( uPAR ) caused a significant reduction in the ability of ATF to induce c fos expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase ( urokinase plasminogen activator , uPA ) and its cell surface receptor ( uPA receptor , uPAR ) play an important role in a variety of physiological and pathological processes requiring cell migration and tissue remodeling . ^^^ Using our syngeneic model of uPAR overexpression by the rat breast cancer cell line Mat B 3 , we have examined the ability of the nonsteroidal antiestrogen , tamoxifen ( TAM ) , and of a selective synthetic inhibitor of uPA , 4 iodo benzo [ b ] thiophene 2 carboxamidine ( B 428 ) , to inhibit expression of uPA and uPAR as well as cell growth , invasion , and metastasis of wild type Mat B 3 cells and of cells overexpressing uPAR ( Mat B 3 uPAR ) . ^^^ These results underscore the utility of anti proteolytic agents ( B 428 ) in addition to standard hormone therapy ( TAM ) in advanced breast cancer patients where the uPA / uPAR system plays a key role in tumor progression . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) is a serine protease that plays a crucial role in blood coagulation and in tumor invasion and metastasis . uPA is a relatively large polypeptide and binds the uPA receptor ( uPAR ) with high affinity and specificity . ^^^ We have produced a fluorescein ( FITC ) labeled human uPA using a conjugation procedure that did not significantly alter its binding characteristics to the uPAR . ^^^ Thirty nM FITC uPA efficiently stains 2 10 10 ( 5 ) uPAR transfected mouse cells in suspension , as determined by flow cytometric analysis . ^^^ One microgram of FITC uPA efficiently stains 2 10 10 ( 5 ) uPAR transfectants grown on slides and analyzed by fluorescence optical microscopy . ^^^ These characteristics allow the use of FITC uPA in both static and dynamic morphological studies of uPAR expressing cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : Using Northern blot analysis , in situ hybridization , and immunohistochemistry , the expression of uPA , its receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and transforming growth factor beta 1 ( TGF beta 1 ) was studied in 14 patients undergoing pancreatic resection for CP . ^^^ RESULTS : Eight of 14 CP samples showed concomitant increased expression ( P < 0 . 001 ) of uPA ( 5 . 2 fold ) , uPAR ( 5 . 9 fold ) , and TGF beta 1 ( 8 . 8 fold ) messenger RNA ( mRNA ) compared with normal controls . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The objectives of this study were to determine the role of TSP 1 and TGF beta 1 in the localization of the plasminogen / plasmin system to the tumor cell surface by the uPA receptor ( uPAR ) and to determine its effect in breast tumor cell invasion . ^^^ Antibodies against uPA or uPAR neutralized the TSP 1 and TGF beta 1 promoted breast tumor cell invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the primary cancers , PAI 2 levels correlated weakly but significantly with those of uPA and PAI 1 , but not with tissue type plasminogen activator ( tPA ) or uPA receptor ( uPAR ) levels . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) bound to a single class of site on VSMCs ( kd , 2 nmol / L ) , binding of pro uPA resulted in a large potentiation of plasmin generation and both were competed by antibodies to the uPA receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Upon clustering of uPA . uPAR complex by a monoclonal antibody , JAK 1 associates with uPAR , which in turn leads to STAT 1 phosphorylation , dimerization , specific binding to DNA , and gene activation . ^^^ Therefore , in this cell line , uPA . uPAR also utilizes the JAK1 / STAT1 pathway for signaling , and gp 130 might be the transmembrane adapter for this signal transduction pathway . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Subsequently , the author cloned the rat uPA receptor ( uPAR ) . uPAR is known to bind the ATF and can permit the uPA molecule to exhibit focal proteolysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The tissue distribution of uPA , tPA , uPA receptor ( uPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) was studied by immunohistochemistry . uPA , tPA , uPAR , and PAI 1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively . ^^^ In addition , in RA tissues , expression of the specific uPA receptor ( uPAR ) and of the plasminogen activator inhibitor type 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MC were found to react with antibodies against tissue type plasminogen activator ( tPA ) and urokinase receptor ( uPAR / CD87 ) , but not with antibodies against urokinase ( uPA ) or plasminogen activator inhibitors ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Enhanced invasion was not associated with significant changes in the expression of uPA or its membrane receptor UPAR ; plasminogen activator inhibitors PAI 1 and PAI 2 ; metalloproteinases MMP 1 , MMP 2 , MMP 3 , MMP 9 and membrane type MMP 1 ; or tissue inhibitors of metalloproteinases TIMP 1 and TIMP 2 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
As implied by the name , uPAR was first identified as a high affinity cellular receptor for urokinase plasminogen activator ( uPA ) . ^^^ In addition to its role in plasminogen activation , compelling evidence has demonstrated a role for uPAR in cell cell and cell extracellular matrix adhesion , both directly and indirectly . uPAR is directly involved in binding to the extracellular matrix molecule , vitronectin , and the affinity of this binding is increased when uPAR is occupied by ( pro ) uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase plasminogen activator ( uPA ) to its specific receptor ( uPAR ) facilitates migration of vascular smooth muscle cells ( VSMC ) . ^^^ We investigated intracellular uPA / uPAR signaling in human aortic VSMC from the cell membrane to the nucleus . uPA binding to VSMC induced a rapid and pronounced increase in tyrosine phosphorylation of several proteins with molecular masses of 53 60 , 85 90 , and 130 140 kDa . ^^^ Our studies therefore suggest that , in VSMC , the uPAR signaling complex utilizes at least two different mechanisms , a direct signaling pathway utilizing the Jak / Stat cascade and a second signal transduction mechanism via Src like protein tyrosine kinases . uPA induced signaling via Jak / Stat is most likely involved in the regulation of cell migration , while the functional purpose of the uPA associated Src PTK activation remains to be elucidated . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The interaction of urokinase type plasminogen activator ( uPA ) with its cell surface receptor ( uPAR ) is implicated in diverse biological processes such as cell migration , tissue remodeling , and tumor cell invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase receptor ( uPAR ) is a receptor for both urokinase plasminogen activator ( uPA ) and the adhesion protein vitronectin . ^^^ There are two forms of cell surface bound uPAR ; intact uPAR and a cleaved form , uPAR ( 2+3 ) , which is formed by uPA catalyzed cleavage of uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Regulation of the uPAR / uPA system expressed on monocytes by the deactivating cytokines , IL 4 , IL 10 and IL 13 : consequences on cell adhesion to vitronectin and fibrinogen . ^^^ Urokinase ( uPA ) and its receptor ( uPAR ) have been proposed to be involved in monocyte migration by inducing degradation of matrix proteins . ^^^ The adhesive function of uPAR depends on a direct interaction with vitronectin which is increased by uPA and by modification of cell surface integrin ( such as CD11b CD 18 ) when associated to uPAR . ^^^ In this study we analysed the role of three deactivating cytokines , IL 4 , IL 10 and IL 13 , on the surface expression of uPA , uPAR and CD11b by monocytes and their consequences on monocyte adhesion to immobilized fibrinogen and vitronectin . ^^^ IL 10 induced a decrease in uPA and CD11b after 18 h incubation and a delayed decrease in uPAR which was only significant after 48 h incubation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These data from the human tumor specimens suggest that increased uPA and uPAr expression may be component of the invasive phenotype of TCC lesions . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present study we measured cathepsin D ( n=162 ) , uPA ( n=116 ) , uPAR ( n=109 ) and PAI 1 ( n=135 ) in tumor cytosols obtained from a population of node negative breast cancer patients . ^^^ A significant correlation was found between levels of uPA , uPAR , and PAI 1 . ^^^ Levels of cathepsin D were directly related to levels of uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Role of urokinase ( uPA ) and its receptor ( uPAR ) in invasion and metastasis of hormone dependent malignancies . ^^^ Along with uPA , its cell surface receptor ( uPAR ) is also believed to be involved due to its ability to recruit uPA within the tumor cell environment . ^^^ In recent years , novel in vivo models of breast and prostate cancer have been developed which have clearly demonstrated the significance of uPA and uPAR in the invasion and metastases of these hormone dependent cancers . ^^^ The availability of these in vivo models has now permitted us to evaluate the molecular , chemical and immunotherapeutic strategies targeted against the uPA / uPAR system . ^^^ This review describes the mechanism of uPA actions in tumor progression and analyses the usefulness of these in vivo models to authenticate uPA / uPAR as a therapeutic target and evaluates the benefits of blocking uPA / uPAR interactions alone or in combination with currently available treatment modalities against this cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A noncatalytic recombinant protein , consisting of amino acids 1 137 of human uPA and the CH 2 and CH 3 regions of mouse IgG 1 ( uPA IgG ) , was expressed , purified , and shown to bind specifically to human uPAR and to saturate the surface of human tumor cells which express uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of this study was to quantify , by Northern analysis , the gene expression of urokinase plasminogen activator ( UPA ) , urokinase receptor ( UPAR ) and plasminogen activator inhibitor type 2 ( PAI 2 ) in human gestational tissues . ^^^ These data are consistent with the hypothesis that , during labour , up regulation of UPAR expression in amnion serves to localize active UPA at the cell surface , thereby increasing proteolytic activity in fetal membranes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Besides the cell surface glycolipid ( GPI ) anchored urokinase receptor ( uPAR ) , which binds uPA with high affinity , recent evidence points to the existence of soluble uPAR ( suPAR ) , as well . ^^^ However , after removal of GPI uPAR with phosphatidylinositol specific phospholipase C , suPAR dose dependently increased uPA binding by fourfold to fivefold . ^^^ Thus , VN mediated uPA binding to cells was regulated by the ratio of soluble to surface associated uPAR . ^^^ In a uPAR deficient cell line ( LM TK ) , suPAR increased uPA binding up to 10 fold , whereas the truncated receptor lacking the amino terminal uPA binding domain was ineffective . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
As interferons ( IFNs ) and dexamethasone can be used together with RA in the treatment of patients with APL , we have now studied the effects of RA together with IFNs and dexamethasone on the plasminogen activation cascade of these cells , including measurement of plasmin generation and uPA receptor ( uPAR ) , using enzyme immunoassays , fluorescence activated cell sorter analysis and RNA extraction with Northern blotting . ^^^ Our main results were : ( 1 ) plasmin was formed on the surface of APL cells ; ( 2 ) RA stimulated transiently plasmin generation and increased uPAR mRNA level ; ( 3 ) IFNs alpha and gamma potentiated RA in its effects on uPA and plasmin activities and on uPAR level ; ( 4 ) dexamethasone suppressed totally the effect of RA on uPA induction and plasminogen activation ; and ( 5 ) IFNs and dexamethasone alone did not have potent effects on plasminogen activation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have investigated the expression and cellular localization of urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator receptor ( uPAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) as well as plasminogen activation in rat liver regeneration by recruitment of progenitor ( oval ) cells . ^^^ Using a model in which surgical partial hepatectomy is combined with feeding of 2 acetylaminofluorene ( 2 AAF ) to induce liver regeneration by proliferation and differentiation of oval cells , expression of uPA , uPAR , and PAI 1 was detected by immunohistochemistry mainly in the duct like formations of expanding oval cells . ^^^ Expression of uPA , uPAR , and PAI 1 , as assessed by immunohistochemical and Northern blot analyses , was also observed , when cells located in and in close proximity to the bile epithelial structures were activated to enter DNA synthesis in response to 2 AAF , and after in vivo infusion of various growth factors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator ( uPA ) to its cellular receptor ( uPAR ) renders the cell surface a favored site for plasminogen activation . ^^^ Recently , a 15 mer peptide antagonist of the uPA uPAR interaction , with an IC 50 value of 10 nM , was identified using phage display technology [ Goodson , R . ^^^ These peptides incorporated covalently into purified soluble uPAR upon photoactivation , and this was inhibited by preincubation with receptor binding derivatives of uPA . ^^^ Since the receptor binding properties of the peptide antagonist closely mimic those of uPA itself , these two ligands presumably share coincident binding site in uPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We present a systematic analysis of the sensitivity and specificity of immunohistochemical stainings for components of the plasminogen activation system , i . e . , uPA , tPA , PAI 1 , PAI 2 , and uPAR , on routinely processed ( formalin fixed , paraffin embedded ) tissues . ^^^ For uPA , PAI 2 , and uPAR , consistent staining results were obtained on paraffin sections . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator ( uPA ) to its receptor , uPAR , regulates cellular adhesion , migration , and tumor cell invasion . ^^^ The amino terminal fragment ( ATF ) of uPA , which binds to uPAR but lacks proteinase activity , also activated ERK 1 and ERK 2 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding is not perturbed by uPA and appears to involve domains DII + DIII of the uPAR protein moiety , but not the glycosylphosphatidylinositol anchor . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Association of urokinase type plasminogen activator ( uPA ) to cells via binding to its specific cellular receptor ( uPAR ) augments the potential of these cells to support plasminogen activation , a process that has been implicated in the degradation of extracellular matrix proteins during cell migration and tissue remodeling . ^^^ The uPA receptor is a glycolipid anchored membrane protein belonging to the Ly 6 / uPAR superfamily and is the only multidomain member identified so far . ^^^ This susceptibility was abrogated when uPAR participitated in a bimolecular complex with pro uPA or smaller receptor binding derivatives thereof , demonstrating the proximity of the ligand binding site to this particular carbohydrate moiety . uPAR preparations devoid of carbohydrate on domain 1 exhibited altered binding kinetics toward uPA ( a 4 6 fold increase in Kd ) as assessed by real time biomolecular interaction analysis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( UPA ) , particularly when bound to its receptor ( UPAR ) , is thought to play a major role in local proteolytic processes , thus facilitating cell migration as may occur during angiogenesis , neointima and atherosclerotic plaque formation , and tumor cell invasion . ^^^ To facilitate understanding of the need and function of the UPA / UPAR interaction in cell migration and vascular remodeling , we changed several amino acid residues in UPA so as to interfere with its interaction with its receptor . ^^^ Since the binding of UPA to UPAR appears to be species specific , we used the differences in amino acid sequences in the growth factor domain of UPA between various species to construct a human UPA variant that does not bind to the human UPAR . ^^^ However , no UPA / UPAR complexes could be observed in cross linking experiments using DFP treated 125I labeled mutant UPA and lysates of various cells , including U 937 histiocytic lymphoma cells , phorbol myristate acetate treated human ECs , and mouse LB 6 cells transfected with human UPAR cDNA . ^^^ In ligand blotting assays , very weak binding of mutant UPA to human UPAR could be observed . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) is a serine protease involved in cancer invasion and metastasis . uPA acts in vivo by binding to a membrane receptor known as uPAR . ^^^ In this study , uPA and uPAR levels were semiquantitated by immunocytochemistry in 36 primary breast carcinomas . ^^^ In contrast , uPAR was only rarely detected in cancer cells and was not detected in normal epithelia surrounding tumour or in areas of adenosis . uPA levels in both stromal and epithelial cells were significantly correlated with those for uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Complexes between urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) were assessed in plasma and serum from 39 breast cancer patients and from 20 healthy individuals , applying a recently developed enzyme linked immunosorbent assay ( ELISA ) for the analysis of these complexes in tumor tissue extracts . ^^^ The assay is based on a combination of rabbit polyclonal anti uPA antibodies for catching and a mouse anti uPAR monoclonal antibody ( MAb ) for detection . ^^^ The specificity of the assessment of uPA : uPAR complexes was verified by simultaneous analysis of the individual blood samples in corresponding non sense ELISA formats , in which either the anti uPA catching antibody or the anti uPAR detecting antibody was substituted with an irrelevant antibody . ^^^ Assessment of native uPA : uPAR complexes was ascertained by demonstrating the absence of any de novo formation of uPA : uPAR complexes in plasma and serum during the sample incubation step in the ELISA , as verified by the use of a peptide antagonist for uPAR . ^^^ Plasma and serum samples contained almost identical levels of uPA : uPAR complexes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To develop a molecule that binds with high affinity to the urokinase ( uPA ) receptor ( uPAR ) on tumor cell surfaces , a bifunctional hybrid molecule [ uPA ( 1 134 ) UTI ( 78 136 ) ] consisting of the uPAR binding NH 2 terminal fragment [ UTI ( 78 136 ) peptide ] of uPA at the NH 2 terminus of UTI ( 78 136 ) peptide was produced in Escherichia coli by genetic engineering . ^^^ Sensitivities of tumor cells towards the anti invasive effect of uPA ( 1 134 ) UTI ( 78 136 ) correlated with the density of uPAR on human tumor cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Treatment of the human fibrosarcoma cell line HT 1080 with diisopropylphosphorofluoridate inactivated uPA ( Dip F uPA ) triggers a cascade of intracellular signals which are mediated by the specific cell surface receptor for uPA ( uPAR ) . ^^^ Of the three uPAR associated kinases , only hck is activated by uPA , whereas no changes in the activities of either fyn or lck could be detected by an in vitro immune complex kinase assay . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase type plasminogen activator ( uPA ) to its receptor ( uPAR ) has been implicated in cancer invasion and metastasis . ^^^ To elucidate the participation of the uPA system in the malignant behaviour of squamous cell carcinoma ( SCC ) in the oral cavity , uPA , uPAR , PAI 1 and 2 expression and localisation in 34 primary oral cancers were examined immunohistochemically . ^^^ The positive rates of uPA , uPAR , PAI 1 and 2 expression were 23 . 5 , 29 . 4 , 29 . 4 and 11 . 8 % , respectively . uPA expression correlated with mode of cancer invasion according to Yamamoto Kohama ' s criteria ( p < 0 . 01 ) and with secondary regional lymph node metastasis . uPAR expression also correlated with mode of invasion . ^^^ In particular , the tumours of both uPA and uPAR positive [ uPA ( + ) / uPAR ( + ) ] cases were highly invasive . ^^^ However , PAI 2 negative cases of uPA ( + ) / uPAR ( + ) were significantly more invasive ( p < 0 . 0001 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Although occupancy of the uPA receptor ( uPAR ) has been shown to alter cellular function and to induce gene expression , the signaling mechanism has not been characterized . ^^^ Analysis by immunoblotting demonstrated tyrosine phosphorylation of focal adhesion kinase ( FAK ) , the focal adhesion associated proteins paxillin and p 130 ( cas ) , and mitogen activated protein kinase ( MAPK ) following the occupancy of the uPAR by uPA . ^^^ Treatment of cells with phosphatidylinositol specific phospholipase C , which cleaves glycosylphosphatidylinositol linked proteins from the cell surface , blocked the uPA induced tyrosine phosphorylation of FAK , indicating the requirement of an intact uPAR on the cell surface . ^^^ Thus , this study demonstrates a novel role for the uPAR in endothelial cell signal transduction that involves the activation of FAK and MAPK , which are mediated by the receptor binding domain of uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To understand the hormonal regulation of the components of the plasminogen plasmin system in human breast cancer , we examined the oestradiol ( E 2 ) regulation of plasminogen activators ( PAs ) , namely urokinase type plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and uPA receptor ( uPAR ) , in our model system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study we analyzed the expression and distribution of the urokinase plasminogen activator ( uPA ) , its membrane receptor ( urokinase plasminogen activator receptor [ uPAR ] ) , and its inhibitor ( plasminogen activator inhibitor 1 [ PAI 1 ] ) in acute necrotizing pancreatitis in human beings . ^^^ METHODS : With immunohistochemistry and Northern blot analysis , the expression and cellular distribution of uPA , uPAR , PAI 1 , and TGF beta 1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis . ^^^ RESULTS : Northern blot analysis showed enhanced expression of uPA , uPAR , and PAI 1 in eight of 12 , seven of 12 , and nine of 12 necrotizing pancreatitis samples , respectively , compared with normal control samples . ^^^ Immunohistochemistry revealed elevated uPA , uPAR , and PAI 1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas . ^^^ In contrast , acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present study , we analyzed the expression of urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) in samples of chronically rejected human kidneys . ^^^ Immunohistochemical analysis in normal kidneys showed weak immunostaining of uPA , moderate to intense uPAR and PAI 1 immunostaining in proximal tubules , and moderate immunostaining in distal tubules , but no signal in the glomeruli or cortical vessels . ^^^ In addition , within the glomeruli of rejected kidney samples , there was positive immunostaining for uPA , uPAR , and PAI 1 in the mesangial cells , but negative staining in most of the endothelial cells , whereas the normal kidneys revealed no immunoreactivity in these structures . ^^^ CONCLUSION : The demonstrated up regulation of uPA / uPAR / PAI 1 in chronic renal rejection is consistent with the plasminogen / plasmin system contributing to tissue remodeling in this disorder . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator ( uPA ) mediates cancer invasion and metastasis by binding to a cell surface receptor ( uPA R , CD 87 ) on both tumor and stromal cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasma urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and urokinase type plasminogen activator receptor ( uPAR ) levels were measured in healthy volunteers and breast cancer patients . ^^^ In pre menopause healthy females , blood was sampled weekly during one menstruation cycle and menstruation phases ( follicular , ovulatory , luteal ) were determined by FSH / LH levels . uPA , PAI 1 , and uPAR levels were at the nadir during ovulatory phase . uPA level was highest at follicular phase while PAI 1 level was highest at luteal phase . ^^^ In comparison between pre and post menopause states , uPA and uPAR levels were higher in post menopause state while PAI 1 level was higher in pre menopause state . ^^^ In breast cancer patients , uPA , PAI 1 , and uPAR positive rates were low when we use the menopause state unmatched cut off points . ^^^ In conclusion , adjustment of physiological changes of uPA , PAI 1 , and uPAR is required in determining pathological elevation of the plasma levels in cancer patients , especially in females . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously shown that thrombospondin 1 ( TSP 1 ) and TGF beta 1 upregulate the urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) and promote tumor cell invasion in breast cancer . ^^^ In this study , we determined the effect of TSP 1 and TGF beta 1 on uPA and uPAR expression and on tumor cell invasion in pancreatic cancer . ^^^ ASPC 1 human pancreatic adenocarcinoma cells were incubated for 48 h on cell conditioned media ( CCM ) either alone ( Control ) or with the addition of either TSP 1 ( 40 micrograms / ml ) or TGF beta 1 ( 5 ng / ml ) . uPA and uPAR expression were determined by ELISA . ^^^ The upper chamber was treated with CCM either alone ( Control ) or with the addition of anti uPA ( 10 micrograms / ml ) or anti uPAR ( 10 micrograms / ml ) . ^^^ TSP 1 and TGF beta 1 induced a twofold increase on uPAR expression but only a slight increase on total uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To determine the role of the uPAR mRNABp on receptor expression , we overexpressed a chimeric beta globin / uPAR / beta globin mRNA containing the 51 nt binding fragment of uPAR mRNA in MS 1 cells and found that uPAR at the cell surface increased by twofold as measured by [ 125I ] uPA binding or ligand blotting . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
FGF 2 stimulated migration was blocked by antibodies against urokinase type plasminogen activator ( uPA ) or uPA receptor ( uPAR ) and by neutralizing anti HGF antibodies . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Cells with low surface urokinase plasminogen activator ( uPA ) and uPA receptor ( uPAR ) were also incapable of intravasation , despite the presence of high levels of MMP 9 . ^^^ We concluded that breaching of the vascular wall is a rate limiting step for intravasation , and consequently for metastasis , and that cooperation between uPA / uPAR and MMP 9 is required to complete this step . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase plasminogen activator ( uPAR ; CD 87 ) is a 50 to 65 kDa glycosylphosphatidylinositol ( GPI ) anchored glycoprotein expressed by leukocytes and tumor cells where it facilitates uPA dependent , plasmin mediated pericellular proteolysis during cellular invasion . ^^^ Whereas the binding of suPAR did not measurably affect cell associated plasmin activation , suPAR did competitively inhibit the binding of exogenous uPA to membrane associated uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Only low levels of uPA receptor ( uPAR ) transcripts were found in trophoblasts and decidual tissue at days 10 . 5 and 11 . 5 p . c . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A marginal inverse correlation was observed between per cent S phase and nm 23 H1 expression ( r = 0 . 193 , P = 0 . 047 ) and a positive correlation was observed between uPA receptor ( uPAR ) and both nm 23 H1 ( r = 0 . 263 , P = 0 . 0018 ) and nm 23 H2 ( r = 0 . 230 , P = 0 . 0064 ) . ^^^ We found no significant differences in Cat D , uPA , PAI 1 or uPAR , as a function of nm 23 expression in either the MDA MB 231 cells or the transfected clones . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Leukocyte adhesion was reconstituted when soluble intact uPAR , but not a truncated form lacking the uPA binding domain , was allowed to reassociate with the cell surface . uPAR ligation with a monoclonal antibody induced adhesion of monocytic cells and neutrophils to vascular endothelium by six to eightfold , whereas ligation with inactivated uPA significantly reduced cell to cell adhesion irrespective of the beta 2 integrin stimulating pathway . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Concomitant with the expression of uPA , an androgen regulated expression of uPA receptor ( uPAR ) was induced . ^^^ These results suggest that the interaction of LNCaP cells with the extracellular matrix plays a dominant role in the androgen control of uPA and uPAR gene expression . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The transcriptional localizations of urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitors ( PAI 1 and PAI 2 ) , which are possibly involved in cancer metastasis , have not been determined in human lung cancer . ^^^ Our results indicate that human non small cell lung cancer cells can autonomously express the mRNAs of uPA , uPAR and PAIs , which are possibly involved in metastasis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It is generated by the cleavage of the proenzyme plasminogen upon the action of the urokinase type plasminogen activator ( uPA ) . uPA is synthesized and secreted by tumor cells and normal cells and interacts with a specific cell surface receptor ( uPAR ) thereby focalizing enzymatic activity to the cell surface . ^^^ Besides its proteolytic activity , uPA in concert with uPAR exert biological effects characteristic for molecules with signal transducing properties including chemotaxis , migration / invasion , adhesion , and mitogenesis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase plasminogen activator ( uPAR ) is a key molecule in cell surface directed plasminogen activation . uPAR binds urokinase plasminogen activator ( uPA ) and thereby focuses plasminogen activation on the cell surface . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have reported previously that both urokinase type plasminogen activator ( uPA ) and its type 1 inhibitor ( PAI 1 ) are statistically significant prognostic variables in patients with high risk breast cancer ( Grondahl Hansen et al . , Cancer Res . , 53 : 2513 2521 , 1993 ) , and we recently described that the uPA receptor ( uPAR ) is a prognostic marker in postmenopausal , node positive breast cancer patients ( Grondahl Hansen et al . , Clin . ^^^ The present retrospective study describes the prognostic impact of uPA , its receptor uPAR , and PAI 1 in breast cancer cytosol from 111 low risk premenopausal patients and 184 low risk postmenopausal patients with a median follow up of 6 . 0 years ( range , 3 . 8 14 . 9 ) and 7 . 4 ( range , 3 . 7 14 . 0 ) years , respectively . uPA , uPAR , and PAI 1 levels were determined by sandwich enzyme linked immunosorbent assays , and data were dichotomized using the median value as the cutoff for calculation of recurrence free survival and overall survival . ^^^ Neither uPA nor uPAR reached statistical significance in the univariate analyses . ^^^ The prognostic value of uPA , uPAR , and PAI 1 was then compared with that of other established prognostic variables by multivariate analysis . ^^^ Neither uPA nor uPAR reached significance in the multivariate analysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Functional assembly of the plasminogen dependent proteolytic system on the cell surface requires multiple interactions involving urokinase ( uPA ) , urokinase receptor ( uPAR ) , plasminogen activator inhibitors , and other molecules that mediate cell migration and adhesion . ^^^ Immunoprecipitation of the preformed cross linked 125I labeled complexes with anti vitronectin , anti uPA , or anti uPAR antibodies revealed that the Mr 82 , 000 and 92 , 000 species do contain ATF and vitronectin and identified the Mr 137 , 000 species as a ternary complex formed by ATF , uPAR , and vitronectin . ^^^ Our findings highlight the ability of uPAR to interact simultaneously with vitronectin and uPA in breast cancer , supporting a dynamic coupling of the molecular mechanisms underlying plasminogen dependent matrix degradation and cell adhesion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Ovarian cancer metastasis is associated with an increase in the urokinase type plasminogen activator ( uPA ) and its receptor uPAR . ^^^ We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV MZ 6 in which endogenous uPA production had been significantly reduced by stable uPA ' antisense ' transfection . ^^^ High molecular weight ( HMW ) uPA , independent of its enzymatic activity , produced an up to 95 % increase in cell number concomitant with 2 fold elevated [ 3H ] thymidine incorporation as did the catalytically inactive but uPAR binding amino terminal fragment of uPA , ATF . uPA induced cell proliferation was significantly decreased by blocking uPA / uPAR interaction by the monoclonal antibody IIIF 10 and by soluble uPAR . ^^^ The efficiency of the uPAR binding synthetic peptide cyclo 19 , 31 uPA 19 31 to enhance OV MZ 6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity . ^^^ Dependence of uPA provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Stable transfectants were analyzed for uPAR mRNA expression , receptor number , in vitro invasion and secretion of uPA and MMP 2 . ^^^ However , the uPAR overexpressing clones and parent cell lines showed similar uPA and MMP 2 activities . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Plasminogen activation by the urokinase type plasminogen activator ( uPA ) is facilitated in the presence of cells expressing the glycolipid anchored high affinity receptor for uPA ( denoted uPAR ) . ^^^ Structures involved in the interaction between human uPAR and a decamer peptide antagonist of uPA binding ( SLNFSQYLWS ) were previously tagged by specific site directed photoaffinity labeling [ Ploug , M . , Ostergaard , S . , Hansen , L . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In contrast , regeneration was not impaired in uPA receptor ( uPAR ) deficient mice at 24 and 44 h . ^^^ Taken together , these data indicate that uPA , independent of its interaction with the uPAR , plays an important role in liver regeneration in vivo . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Although urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) may enhance matrix degradation as well as migration and invasion by smooth muscle cells ( SMCs ) , their roles in cell adhesion are uncertain . ^^^ Therefore , we examined the ability of uPA and uPAR to modulate adhesion of cultured human vascular SMCs to various matrices . ^^^ These data suggest that uPA stimulates adhesion of SMCs specifically to vitronectin and that it is mediated by an interaction with uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present study examined mechanisms underlying this phenotypic change by investigating the effects of asbestos on transcription factor activation and expression of urokinase type plasminogen activator ( uPA ) and its receptor uPAR . ^^^ Immunocytochemistry showed that chrysotile stimulated uPA activity was associated with a time dependent augmentation of uPAR protein levels . ^^^ This response to asbestos was not limited to endothelial cells , since both uPA and uPAR mRNA levels increase in human bronchial epithelial BEAS 2B cells exposed to chrysotile fibers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) are important in the regulation of tumor tissue progenesis , cell differentiation , tumor cell motility , and tumor cell invasiveness . ^^^ We have recently reported that the levels of uPA and uPAR were higher in malignant astrocytomas than in low grade gliomas . ^^^ In the present study , we measured the levels of uPA and uPAR during the growth of glioblastomas in nude mice . ^^^ In addition , immunohistochemical staining for uPA and uPAR revealed strong immunoreactivity in tumor cells with the staining more intense on day 28 than on day 14 . ^^^ These results suggest that the upregulation of uPA and uPAR plays a major role in the formation of gliomas . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The malignant phenotype of prostatic tumor cells correlates with the expression of both uPA and its cell membrane receptor ( uPAR ) ; however , there is little information concerning the role of cell bound uPA in matrix degradation and invasion . ^^^ In addition , we provide direct evidence that both uPA secretion and the presence of uPA uPAR complexes characterize the invasive phenotype of PRCA cells and suggest the existence of several pathways by which tumor cells acquire plasmin activity . ^^^ LNCaP cells ( which do not produce uPA but express uPAR ) may activate plasmin through exogenous uPA . ^^^ Plasmin activation and triggering of the proteolytic cascade involved in Matrigel invasion is blocked by antibodies against uPA ( especially by anti A chain of uPA which interacts with uPAR ) and by PA inhibitors such as p aminobenzamidine which may regulate levels of cell bound uPA . uPA may also regulate growth in PRCA cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of the zymogenic form of urokinase type plasminogen activator ( pro uPA ) to its specific cellular receptor , uPAR , leads to a large potentiation of plasmin generation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Tumor hypoxia and high levels of expression of the urokinase type plasminogen activator ( uPA ) receptor ( uPAR ) represent a poor clinical outcome for patients with various cancers . ^^^ Increased uPAR expression was paralleled by higher cell associated uPA levels and lower levels of secreted uPA as determined by gel zymography performed on cell extracts and culture conditioned media . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and matrix metalloproteinases ( MMPs ) 1 and 9 are considered to play important roles in cancer invasion and metastasis . ^^^ Stromal expression of uPAR and macrophage number in intestinal type were higher in patients without liver metastasis than in patients with liver metastasis , while uPA expression in cancer cells was more pronounced in patients with liver metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We examined whether two newly defined parameters , the density of urokinase type plasminogen activator ( uPAD ) and the density of its receptor ( uPARD ) , which were determined by dividing the serum levels of uPA and uPAR by the prostate volume , respectively , could be used as predictors of the progression and prognosis of prostate cancer ( PC ) . ^^^ Serum levels of uPA and uPAR in 40 healthy controls , 70 patients with benign prostatic hypertrophy ( BPH ) and 80 patients with PC were measured by a sandwich enzyme immunoassay , and prostate volume was measured by ultrasonography . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MC were examined by Giemsa staining and by immunohistochemistry using antibodies against tryptase , chymase , tissue type plasminogen activator ( tPA ) , urokinase ( uPA ) , urokinase receptor ( uPAR ) , and plasminogen activator inhibitors ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Finally , the expression of both urokinase plasminogen activator ( UPA ) and its receptor ( UPAR ) were induced after TPA treatment by 8 and 7 fold , respectively . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To determine whether urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) directly modulate the migration of brain tumor cells , we examined six human brain tumor cell lines , 2 astrocytomas ( SW 1088 , SW 1783 ) , 2 medullobastomas ( Daoy , D341Med ) , and 2 glioblastomas ( U87MG , U118MG ) , for their surface uPAR expression , endogenous PA activity , and functional proteolytic activity by an ECM degradation assay . ^^^ Migration on Transwell membranes and invasion of Matrigel was then tested by pre incubating the cells with increasing concentrations of either uPA , the proteolytically inactive amino terminal fragment ( ATF ) of uPA , or the uPAR cleaving enzyme , phosphatidylinositol specific phospholipase C ( PI PLC ) . ^^^ All of the cell lines , except D341Med , express surface uPAR protein and uPA activity . ^^^ High levels of uPAR and uPA activity correlated with cellular degradation of ECM , cell migration , and Matrigel invasion . ^^^ We conclude that ligation of uPAR by uPA directly induces brain tumor cell migration , independent of uPA mediated proteolysis ; and in concert with ECM degradation , markedly enhances invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we characterized the effects of the VLDLr on the internalization , catabolism , and function of the uPA receptor ( uPAR ) in MCF 7 and MDA MB 435 breast cancer cells . ^^^ In the absence of exogenous agents , the uPAR catabolism t ( 1 ) / ( 2 ) was 8 . 2 h . uPA . ^^^ PAI 1 complex accelerated uPAR catabolism ( t ( 1 ) / ( 2 ) to 1 . 8 h ) , while RAP inhibited uPAR catabolism in the presence ( t ( 1 ) / ( 2 ) of 7 . 8 h ) and absence ( t ( 1 ) / ( 2 ) of 16 . 9 h ) of uPA . ^^^ The effects of RAP on MCF 7 cell motility were entirely abrogated by an antibody which binds uPA and prevents uPA binding to uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Antisense uPAR inhibition decreased uPAR expression by 48 66 % and cell associated urokinase plasminogen activator ( uPA ) by 30 68 % . ^^^ Additionally , antisense uPAR inhibition induced a 68 70 % reduction in uPA and plasmin activities . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present paper we first compared the expression levels of uPA , tPA , PAI 1 and uPAR in a compound group consisting of 33 cancer lesions of various origin ( breast , lung , colon , cervix and melanoma ) as quantitated by ELISA and semi quantitated by IHC . ^^^ Spearman correlation coefficients between IHC results and ELISA results for uPA , tPA , PAI 1 and uPAR varied between 0 . 41 and 0 . 78 , and were higher for the compound group and the breast cancer group than for the melanoma group . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
High levels of uPA or of its receptor ( uPAR , CD 87 ) are produced in human cancers and are strong prognostic indicators of relapse . ^^^ Thus uPA and uPAR have a profound influence on cell migration . ^^^ Chemotaxis is induced through an uPA dependent conformational change in uPAR which uncovers a very potent chemotactic epitope acting through a pertussis toxin sensitive step and activating intracellular tyrosine kinases . ^^^ Binding of uPA transforms uPAR from a receptor for uPA into a pleiotropic ligand ( `` activated uPAR ' ' ) for other still unidentified surface molecules . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In human cancers the components of matrix degrading protease systems ( uPA , uPAR , PAI 1 and MMPs ) can be expressed by either the non neoplastic stromal cells , the cancer cells or both . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The active process of pericellular proteolysis is central in tumor invasion , and in particular the essential role of the urokinase type plasminogen activator ( uPA ) is well established . uPA mediated plasminogen activation facilitates cell migration and invasion through extracellular matrices by dissolving connective tissue components . uPA , its receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) are enriched in several types of tumors . ^^^ Ex vivo studies have shown that uPAR , uPA and its inhibitors can be found on the surface of normal blood cells and on the blast cell surfaces from patients with acute leukemia as well as from plasma samples . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of urokinase ( uPA ) and urokinase receptor ( uPAR ) was analyzed in 137 non small cell lung carcinomas by immunohistochemistry . ^^^ No relationship could be observed between the proliferative activity of the carcinomas measured by flow cytometry and the expressions of uPA and uPAR . ^^^ In addition , there was no association of the expressions of uPA or uPAR and vessel density ( angiogenesis ) , neither any significant correlation between the expressions of uPA or uPAR and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Like urokinase ( uPA ) , Zn2+ increased the binding of radiolabeled VN to uPAR expressing cells , as well as the interaction of VN with immobilized uPAR in an isolated system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Several investigators have revealed that urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) are overexpressed in serum as well as in tumor tissues in patients with various types of cancer . ^^^ In this study , we examined whether the serum levels of uPA and uPAR could be used as predictors of the progression and prognosis of prostate cancer . ^^^ METHODS : Serum levels of uPA and uPAR in 54 healthy controls , 62 patients with benign prostatic hypertrophy ( BPH ) , and 72 patients with prostate cancer were measured by a sandwich enzyme immunoassay . ^^^ RESULTS : The mean serum levels of uPA and uPAR in patients with prostate cancer were significantly higher than those in healthy controls and patients with BPH . ^^^ Furthermore , the serum uPA and uPAR levels in prostate cancer patients with metastasis were significantly elevated compared with those in patients without metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present study compares plasma urokinase plasminogen activator ( uPA ) peptide levels , plasma plasminogen inhibitor ( PAI 1 ) activity and urokinase receptors ( uPAR ) on peripheral blood monocytes of patients with stable coronary artery disease ( SCAD ) and healthy volunteers . 2 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Adenovirus mediated delivery of a uPA / uPAR antagonist suppresses angiogenesis dependent tumor growth and dissemination in mice . ^^^ This defective adenovirus was used in three murine models to assess the antitumoral effects associated with local or systemic delivery of ATF , a broad cell invasion inhibitor that antagonizes uPA binding to its cell surface receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we examined the levels of both uPA and uPAR in human gingival fibroblasts treated with Porphyromonas gingivalis lipopolysaccharide ( LPS ) . ^^^ LPS increased the protein and mRNA levels of both uPA and uPAR in gingival fibroblasts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The 55 kD urokinase ( uPA ) receptor ( uPAR , CD 87 ) is capable of binding uPA and may be involved in regulating cell associated plasminogen activation and pericellular proteolysis . ^^^ While investigating the relationship between uPAR levels and plasmin generation , we found that uPA catalyzed plasminogen activation is stimulated by cells which do not express uPAR . ^^^ A mechanism is proposed whereby uPA can associate with binding sites on the cell surface of lower affinity , but higher capacity than uPAR , but these are sufficient to stimulate plasmin generation even at subphysiologic uPA concentrations . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Particular attention has been given to the effects of plasmin proteolysis which is generated in the extracellular matrix by urokinase plasminogen activator ( uPA ) complexed with its receptor ( uPAR ) . ^^^ The paper also discusses the usefulness of the markings of the substances under discussion for diagnostic prognostic purposes , and a perspective of using the new research in therapy , for example , by using antibodies anti uPA and anti uPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Compared to controls the uPA antigen levels in patient plasmas were elevated and decreased along with uPAR during treatment . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) participate in matrix degradation and cell migration by focusing proteolysis and functioning as a signaling ligand / receptor complex . uPAR , anchored by a lipid moiety in the membrane , is thought to require a transmembrane adapter to transduce signals into the cytoplasm . ^^^ To study uPAR signaling , we transfected the prostate carcinoma cell line LNCaP , which does not express endogenous uPA or uPAR , with a uPAR encoding cDNA , resulting in high level surface expression . ^^^ Ligation of uPAR with uPA or its amino terminal fragment enhanced haptotactic migration to fibronectin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
However , migration of hSMC was promoted by r uPA and not by r uPAmut . r uPA induced migration occurred at concentrations ( half maximally effective concentration of 2 nM ) approximating the Kd for uPA uPAR binding ( 1 nM ) . r uPA induced migration was not affected by the plasmin inhibitor aprotinin . ^^^ Since the [ 3H ] thymidine incorporation response to each isoform occurred at concentrations ( > 50 nM ) much higher than necessary for uPAR saturation by ligand ( 1 nM ) , this mitogenic response may be independent of binding to uPAR . [ 3H ] thymidine incorporation responses to r uPA and uPAmut were sensitive to the plasmin inhibitor aprotinin , and uPA stimulated DNA synthesis was inhibited by plasminogen activator inhibitor . ^^^ We conclude that hSMC migration in response to uPA depends upon on its binding to uPAR , whereas uPA stimulated DNA synthesis in these cells requires proteolysis and plasmin generation . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we demonstrate that uPA stimulates migration of MCF 7 breast cancer cells , HT 1080 fibrosarcoma cells , and uPAR overexpressing MCF 7 cells by a mechanism that depends on uPA receptor ( uPAR ) ligation and ERK activation . ^^^ Thus , we have demonstrated that uPA promotes cellular migration , in an integrin selective manner , by initiating a uPAR dependent signaling cascade in which Ras , MEK , ERK , and MLCK serve as essential downstream effectors . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We review the evidence in support of the notion that , upon experimental oncogenic transformation or in spontaneous human cancers , mitogenesis and expression of urokinase ( uPA ) and its receptor ( uPAR ) are activated through common signaling complexes and pathways . ^^^ It is well documented that uPA , uPAR or metalloproteinases ( MMPs ) are overexpressed in tumor cells of mesenchymal or epithelial origin and these molecules are required for tumor invasion and metastasis . ^^^ Cells from human tumors or oncogene transformed cells overexpress uPA and uPAR , and also show a sustained activation of the above mentioned signaling modules . ^^^ In this paper we show that the classical mitogenic pathway involving Ras Erk , PKC Erk or Rac JNK , among others , is activated by growth factors or endogenously by oncogenes , and constitutively activates uPA and uPAR expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Macrophages concentrate urokinase type plasminogen activator ( uPA ) at the cell surface by expressing urokinase receptors ( uPAR ) in order to focus the pericellular space plasminogen dependent proteolysis important in matrix remodeling and cell movement . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and uPA receptor ( UPAR ) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors . ^^^ Our results support the therapeutic potential of targeting the uPA uPAR system for the treatment of gliomas and other cancers . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To test this hypothesis , we analyzed the production of urokinase type plasminogen activator ( uPA ) , and its receptor ( uPAR ) , 2 molecules involved in the invasive phenotype , in cells over expressing RGD wild type FN ( FNwt clones ) or RGD mutated FN ( FN RGD minus clones ) . ^^^ Furthermore , treatment of the parental cell line as well as the control and FN expressing clones with exogenous purified FN or RGD peptides induced up regulation of uPA production and the reduction of uPA membrane binding , which was associated with lower expression of uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Because of a surface bound uPA receptor ( uPAR ) , expressed by some cell types ( for example , macrophages , malignant cells and inflammatory activated synoviocytes ) , the action of uPA can be localised and intensified . uPAR seems to have a role in the mechanisms leading to invasive growth of malignant tissue and the rheumatoid pannus . uPAR may become cleaved at its cell surface anchor , thus forming a free soluble receptor ( suPAR ) . suPAR is detectable in low but constant values in plasma of healthy people , while increased concentrations are found in patients with disseminated malignant disease , so that suPAR may be an indicator of invasive growth and tissue remodelling . suPAR concentrations in plasma have not previously been measured in rheumatic patients . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In contrast , both mRNA and protein levels for the uPA receptor ( uPAR ) were increased by treatment with concentrations of chromium ( 6 ) that did not completely inhibit protein synthesis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Treatment of cells with agents that abrogate uPA receptor ( uPAR ) function , including neutralizing anti uPAR antibody , phosphatidylinositol specific phospholipase C , or a selective antagonist that blocks the association of uPA with uPAR ( A 5 compound ) , all failed to prevent uPA induced tyrosine phosphorylation . ^^^ These results demonstrate that , in H 157 cells , uPA induces tyrosine phosphorylation of a 78 kDa protein via a proteolysis dependent but uPAR independent mechanism . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its specific receptor ( uPAR ) act in concert to stimulate cytoplasmic signaling machinery and transcription factors responsible for cell migration and proliferation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In vitro studies have demonstrated that the binding of urokinase type plasminogen activator ( uPA ) to its cell surface receptor ( uPAR ) greatly accelerates plasminogen activation . ^^^ Knowing that uPA binding to uPAR is species specific , we used adenoviral vectors to transfer human or murine uPA genes into human or mouse epithelial cells in vitro and to mouse lungs in vivo . ^^^ A monoclonal antibody that blocks the binding of human uPA to human uPAR suppressed fibrin degradation by human cells expressing human uPA but not murine uPA . ^^^ These results show that uPA bound to uPAR increases the efficiency of fibrinolysis on epithelial cell surfaces in a biologically relevant fashion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Experiments have demonstrated that some other components , except UPA itself , can be very important in this process , including UPA receptor ( UPAR ) and UPA inhibitors PAI 1 and PAI 2 . ^^^ Clinical retrospective studies using predominantly ELISA techniques have shown that the high levels of UPA , PAI 1 and UPAR in the tumor tissue are associated with poor prognosis both for overall and for disease free survival of breast cancer patients , and the elevated level of PAI 2 may be indicative of better survival . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In gastric cancer , overexpression of the receptor ( uPAR or CD 87 ) for the serine protease urokinase type plasminogen activator ( uPA ) in disseminated cancer cells indicates shorter survival of cancer patients . ^^^ Next , CD 87 in tumor cells is identified by chicken antibody HU 277 to the uPA receptor and goat anti chicken IgY labeled with fluorochrome Alexa 568 ( excitation wavelength 568 nm ) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PURPOSE : To study interactions between disease free survival ( DFS ) and four components of the plasminogen activator system : urokinase type plasminogen activator ( uPA ) , its two inhibitors ( PAI 1 and PAI 2 ) , and its membrane receptor uPAR . ^^^ PATIENTS AND METHODS : We conducted a retrospective study of 499 primary breast cancer patients ( median follow up , 6 years ) . uPA , PAI 1 , and PAI 2 were determined on cytosols and uPAR on solubilized pellets , using enzyme linked immunoadsorbent assay kits ( American Diagnostica , Greenwich , CT ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We found that uPA / uPAR proteins were physically associated with alpha5beta1 , and that in cells with low uPAR the frequency of this association was significantly reduced , leading to a reduced avidity of alpha5beta1 and a lower adhesion of cells to the fibronectin ( FN ) . ^^^ Compared with uPAR rich tumorigenic cells , the basal level of active extracellular regulated kinase ( ERK ) was four to sixfold reduced in uPAR poor dormant cells and its stimulation by single chain uPA ( scuPA ) was weak and showed slow kinetics . ^^^ These results indicate that dormancy of low uPAR cells may be the consequence of insufficient uPA / uPAR / alpha5beta1 complexes , which can not induce ERK1 / 2 activity above a threshold needed to sustain tumor growth in vivo . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator receptor ( uPAR ) is a membrane anchored protein with urokinase plasminogen activator ( uPA ) as the ligand . ^^^ This immunohistochemical study shows the localization of uPA and uPAR in a prospective design with stereological sampling of fetal and maternal tissue from normal , ectopic and hydatidiform molar ( HM ) pregnancies . ^^^ The corresponding proliferating IT with cytological atypia sprouting from the chorionic villi in HM was uPAR negative . uPA but not uPAR was observed in anchoring distal IT at the attachment point to the basal plate . ^^^ In the placental bed , extravillous interstitial trophoblasts were uPA positive but uPAR negative . ^^^ The trophoblast giant cells were both uPA and uPAR negative . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We examined , using recombinant wild type and mutated forms of uPA , the extent to which its proteolytic properties , its growth like domain ( GFD ) and / or interactions with the specific receptor ( uPAR ) contribute to the chemotactic activity towards vascular smooth muscle cells ( SMC ) . ^^^ These results indicate that additional mechanisms , not dependent on uPA ' s proteolytic activity or the binding ability of its GFD to uPAR , are the major contributors to its chemotactic action on SMC . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To test this hypothesis , we used complementary techniques in rabbit and human mesothelial cells to determine whether uPAR expression is altered by exposure to asbestos . uPAR expression was induced by chrysotile and crocidolite asbestos , but not by wollastonite , as indicated by binding of radiolabeled urokinase type plasminogen activator ( uPA ) to rabbit or human mesothelial cells . uPA was not induced by fiber exposure . ^^^ Exposure to exogenous uPA increased uPA activity of cells exposed to wollastonite but not asbestos treated MeT5A cells . uPAR expression increased further when asbestos was preincubated with vitronectin ( VN ) or serum . ^^^ Increases in uPAR expression were confirmed by binding of uPA to uPAR in cell membrane preparations and immunofluorescent staining of uPAR at the cell surface , and were associated with increases in steady state uPAR messenger RNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
TPA treatment also causes secretion of urokinase type plasminogen activator ( uPA ) and expression of its receptor ( uPAR ) , which activates plasminogen to plasmin and may digest extracellular domains of desmosomes and hemidesmosomes . ^^^ Binding of PV IgG to Dsg 3 induces activation of diverse isoenzymes of PKC , linked to uPA secretion and uPAR expression . ^^^ This PV IgG induced Dsg 3 phosphorylation and Dsg 3 deletion from desmosomes may impair desmosome formation , whereas PV IgG induced PKC signaling mediates the uPA secretion and uPAR expression leading to digestion of preexisting desmosomes from the outside of the cell . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Gene expression for plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase and tissue plasminogen activators ( uPA and tPA ) , urokinase plasminogen activator receptor ( uPAR ) , and transforming growth factor beta 1 ( TGF beta 1 ) was examined by Northern analysis . ^^^ Western analysis was performed to detect protein expression of PAI 1 , uPA and uPAR . ^^^ RESULTS : At 6 weeks , when fibrosis had occurred , uPA and uPAR mRNAs had increased 2 . 8 fold and 1 . 8 fold , respectively ; PAI 1 and tPA mRNA levels were unchanged . ^^^ At the cirrhotic stage ( 9 to 12 weeks ) , mRNA levels for PAI 1 , uPA , uPAR and tPA were all increased . ^^^ Western analysis also showed increased uPA and uPAR expressions in fibrotic liver , and increased PAI 1 , uPA and uPAR expressions in cirrhotic liver . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We investigated the production by leukaemic cells of plasminogen activators [ urokinase ( uPA ) and tissue type PA ( tPA ) ] , cell surface receptor for uPA ( uPAR ) and PA inhibitors ( PAI 1 and PAI 2 ) . ^^^ High levels of uPA mRNA were found in M 1 , M 2 , M 3 and M 4 M5 AMLs , whereas tPA mRNA was not detected in any of the analysed cases . uPAR mRNA was confined to subtypes M 4 M5 . ^^^ The finding of uPA , uPAR , PAI 1 and PAI 2 synthesized by leukaemic cells suggests that plasminogen activation may contribute to the invasive behaviour of these cells , the fibrinolytic imbalance observed in leukaemic patients and the differentiation and proliferation of M 4 M5 by interaction of uPA with uPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Selectively cross linking uPA occupied uPAR with an anti uPA mAb produced smaller increases in [ Ca2+ ] 1 , but fully saturating uPAR with exogenous uPA enhanced the [ Ca2+ ] 1 response to equal the effect of aggregating uPAR directly . ^^^ These results indicate that uPAR aggregation initiates phosphoinositide hydrolysis by mechanisms that are not strictly dependent on associated uPA or CR3 . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The LRP deficient cells demonstrated increased levels of cell surface uPAR , higher levels of uPA in conditioned medium , increased migration on vitronectin coated surfaces , and increased invasion of Matrigel . ^^^ Antibodies which block binding of endogenously produced uPA to uPAR reduced ERK phosphorylation and migration of LRP deficient cells to the levels observed with control cells . ^^^ These studies demonstrate that binding of endogenously produced uPA to uPAR may serve as a major determinant of basal levels of activated ERK and , by this mechanism , regulate cellular migration and invasion . ^^^ By regulating the uPA / uPAR system , LRP may also regulate ERK activation , cellular migration , and invasion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Considering recent findings that both urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitors ( PAIs ) are involved in tumor growth through an urokinase type plasminogen activator ( uPA ) activity independent mechanism , the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated . ^^^ RESULTS : All uPAR , uPA , PAI 1 , and PAI 2 antigen levels in tumor tissue were significantly higher than those in normal tissue . ^^^ Significant positive correlation coefficients ( r ) were obtained between tumor size and the calculated ratios of PAI 1 / uPAR ( r = 0 . 490 ; P < 0 . 0001 ) and PAI 1 / uPA ( r = 0 . 469 ; P < 0 . 0001 ) . ^^^ CONCLUSIONS : Higher expression of uPAR was related to poor prognosis of patients with colorectal carcinoma and excess amounts of PAI 1 over uPAR or uPAR bound uPA appeared to play an important role in tumor progression . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MATERIALS AND METHODS : In the present study , we determined the plasma concentrations of tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , PAI 2 , and uPA receptor ( uPAR ) in 25 patients with ovarian cancer , 16 patients with benign gynecologic tumor or inflammation , and 36 healthy controls in order to find out whether the plasma levels of these markers could be used to evaluate the prognostic value in patients with gynecologic cancers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Urokinase ( uPA ) and the urokinase receptor ( uPAR ) form a multifunctional system capable of concurrently regulating pericellular proteolysis , cell surface adhesion , and mitogenesis . ^^^ The role of uPA and uPAR in directed proteolysis is well established and its function in cellular adhesiveness has recently been clarified by numerous studies . ^^^ The molecular mechanisms underlying the mitogenic effects of uPA and uPAR are still unclear , however . ^^^ Immunoprecipitation experiments in combination with an in vitro kinase assay demonstrated a specific association of uPAR with nucleolin and casein kinase 2 and revealed a uPA induced activation of casein kinase 2 , which presumably led to phosphorylation of nucleolin . ^^^ CONCLUSIONS : We conclude that in human vascular smooth muscle cells , uPA induces the formation and activation of a newly identified signaling complex comprising uPAR , nucleolin , and casein kinase 2 , that is responsible for the uPA related mitogenic response . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Guided by these results we have now performed an alanine scanning analysis of this region in uPAR by site directed mutagenesis and subsequently measured the effects thereof on the kinetics of uPA binding in real time by surface plasmon resonance . ^^^ Only four positions in loop 3 of uPAR domain 1 exhibited significant changes in the contribution to the free energy of uPA binding ( DeltaDeltaG > / = 1 . 3 kcal mol ( 1 ) ) upon single site substitutions to alanine ( i . e . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its cell surface receptor ( uPAR ) have been shown to be expressed in macrophages in atherosclerotic arterial walls , but the regulatory mechanisms of their expression remain unclear . ^^^ The present study was performed to examine the effects of lysophosphatidylcholine ( lysoPC ) , an important atherogenic lipid , on the expression of uPA and uPAR in human monocyte derived macrophages . ^^^ LysoPC upregulated the mRNA expression of uPA and uPAR , and it increased the protein expression of uPA in the culture medium and bound to the cell surface and of uPAR in the particulate fraction of the cells . ^^^ The combined incubation with reduced glutathione diethyl ester or N acetylcysteine , antioxidants , suppressed the upregulation of uPA and uPAR mRNA and the increase in plasminogen activator activity by lysoPC . uPA and uPAR mRNA expression was also induced by the incubation with xanthine and xanthine oxidase , a superoxide anion generating system . ^^^ The results suggest that lysoPC increased the expression of uPA and uPAR and their functional activities in human monocyte derived macrophages , at least in part through a redox sensitive mechanism . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) play an important role in tumour invasion . ^^^ Previous studies have shown by RT PCR that uPA and uPAR mRNAs are expressed in human hepatocellular carcinoma ( HCC ) . ^^^ Here , in situ hybridization , immunohistochemistry , and double immunofluorescence were used to identify the cells expressing uPA and uPAR in 26 HCCs . ^^^ The results indicate that uPA and uPAR were expressed in every case , almost exclusively in stromal cells , mostly myofibroblasts and macrophages , except for rare tumoural hepatocytes expressing cytokeratin 7 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
HGF / SF induces the expression of urokinase plasminogen activator ( uPA ) and the uPA receptor ( uPAR ) , important mediators of cell invasion and metastasis . ^^^ We have developed a cell based assay to screen for inhibitors of this signaling system using the induction of endogenous uPA and uPAR and the subsequent conversion of plasminogen to plasmin as the biological end point . ^^^ Assay validation was established using a neutralizing antiserum to HGF / SF and a uPA inhibitor ( B 428 ) , as well as inhibitors of the MKK MAPK1 / 2 pathway , shown previously to be important in the induction of uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present study involving 2780 patients with primary invasive breast cancer , we have evaluated the prognostic importance of the four major components of the uPA system [ uPA , the receptor uPAR ( CD 87 ) , and the inhibitors PAI 1 and PAI 2 ] . ^^^ The levels of the four factors significantly correlated with each other ; the Spearman rank correlation coefficients ( r ( s ) ) ranged from 0 . 32 ( between PAI 2 and PAI 1 or uPAR ) to 0 . 59 ( between uPA and PAI 1 ) . ^^^ In the multivariate analyses for relapse free survival ( RFS ) and overall survival ( OS ) , we defined a basic model including age , menopausal status , tumor size and grade , lymph node status , adjuvant therapy , and steroid hormone receptor status . uPA , uPAR , PAI 1 , and PAI 2 were considered as categorical variables , each with two cut points that were established by isotonic regression analysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator receptor ( uPAR ) has been identified some 15 years ago and the anticipation was that its presence on the cell surface will provide a focus for anchoring uPA and possibly protect the enzyme from native inhibitors . ^^^ The studies of the last decade have shown that uPA localized to the surface of cells by uPAR is indeed an important factor in the process of cancer cell invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Keratinocyte activation comprises changes in protein and gene expression pattern resulting in phenotypic and functional changes necessary for re epithelialization such as the expression of urokinase type plasminogen activator ( uPA ) and its cell surface receptor ( uPA R ; CD 87 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of the urokinase plasminogen activator ( uPA ) to its receptor ( uPAR ) regulates cell adhesion , surface proteolysis , chemotaxis and cell extravasation in a number of experimental systems . ^^^ Indeed , it is likely that upon binding to uPA , uPAR undergoes a conformational change that uncovers a new epitope located in the linker region between domain 1 and 2 of the receptor and is endowed with a potent chemotactic activity . ^^^ We have shown that chymotrypsin cleaves uPAR between domain 1 and 2 in an area that can be also cleaved by uPA at high efficiency and generate a receptor that can mediate monocytes migration independently of uPA binding . ^^^ These studies indicate that in addition to its receptor function , upon binding to uPA , uPAR becomes a pleiotropic ligand for other still to be identified surface molecules . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the solid tumor , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and uPA receptor ( uPAR ) are considered as prognostic factors . ^^^ In this study , we have investigated whether secretion of the uPA , PAI 1 and uPAR from the primary breast cancer tissue can be detected in the blood of the patients using the ELISA assay . ^^^ We have found that the plasminogen activation system ( uPA , PAI 1 , uPAR ) of tumor tissue is activated from the early stage of breast cancer . ^^^ The blood level of the plasminogen activation system correlated with that of tissue in an order of uPAR ( r ( 2 ) =0 . 61 ; P=0 . 001 ) , uPA ( r ( 2 ) =0 . 35 ; P=0 . 001 ) and PAI 1 ( r ( 2 ) =0 . 11 ; P=0 . 001 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Thus , the uPA / uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The regulatory mechanisms underlying the overexpression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in highly invasive breast carcinomas remain poorly understood . ^^^ Finally , the engagement of uPAR by catalytically inactive uPA in the MDA MB 231 breast carcinoma cell line results in a rapid up regulation of Sp 1 binding activity followed by an increase of uPAR protein . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) is thought to exert its effects on cell growth , adhesion , and migration by mechanisms involving proteolysis and interaction with its cell surface receptor ( uPAR ) . ^^^ R uPAwt induced chemotaxis was dependent on an association with uPAR and a uPA kringle domain binding site , determined using a monoclonal uPAR antibody to prevent the uPA uPAR interaction , and a monoclonal antibody to the uPA kringle domain . ^^^ Specific binding of r uPA ( H / Q ) GFD to hAWSMC involved an interaction with a single site whose characteristics were similar to those of the low affinity site of r uPAwt binding to hAWSMC . uPAR deficient HEK 293 cells specifically bound r uPAwt and r uPA ( H / Q ) GFD via a single , similar type of binding site . ^^^ HEK 293 cells transfected with the uPAR cDNA expressed two classes of sites that bound r uPAwt ; however , only a single site was responsible for the binding of r uPA ( H / Q ) GFD . ^^^ Together , these findings indicate that uPA induced chemotaxis is dependent on the binding of the uPA kringle to the membrane surface of cells and the association of uPA with uPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Plasminogen activator inhibitor type 2 ( PAI 2 ) is a member of the serine protease inhibitor ( SERPIN ) superfamily and forms stable complexes with urokinase type plasminogen activator ( uPA ) . uPA can be found on the cell surface attached to its specific receptor ( uPAR ) , allowing for controlled degradation of the extracellular matrix by the activation of plasminogen into plasmin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Double immunofluorescence is performed using antibodies against cytokeratins 8 / 18 / 19 ( mAb A45B / B3 ) and the uPA receptor CD 87 ( pAb HU 277 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Overexpression of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) has been well documented in a wide variety of tumor cells . ^^^ In breast cancer , expression of uPA / uPAR is essential for tumor cell invasion and metastasis . ^^^ However , the mechanism responsible for uPA / uPAR expression in cancer cells remains unclear . ^^^ Treatment of highly invasive BT 549 cells with a specific p 38 MAPK inhibitor SB 203580 diminished both uPA / uPAR mRNA and protein expression and abrogated the ability of these cells to invade matrigel , suggesting that p 38 MAPK signaling pathway is involved in the regulation of uPA / uPAR expression and breast cancer cell invasion . ^^^ We also demonstrated that SB 203580 induced reduction in uPA / uPAR mRNA expression resulted from the de stabilization of uPA and uPAR mRNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator , uPA , when bound to its specific receptor , uPAR ( CD 87 ) , plays a significant role in tumor cell invasion and metastasis . ^^^ We explored , whether suPAR / uPA interaction reduces the binding of uPA to cell surface associated uPAR , and , as a consequence , could suppress tumor growth and metastasis of the human breast cancer cell line MDA MB 231 BAG . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of urinary type plasminogen activator ( uPA ) and its receptor ( uPAR ) is correlated with matrix proteolysis , cell adhesion , motility , and invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) binds to its receptor ( uPAR ) with a K ( d ) of about 1 nm . ^^^ In the present study , we show that uPA and recombinant soluble uPAR ( suPAR ) , at concentrations that exceed the K ( d ) and the theoretical saturation levels ( 10 80 nm ) , establish novel interactions that lead to a further increase in the activity of the single chain uPA ( scuPA ) / suPAR and two chain uPA ( tcuPA ) / suPAR complexes . ^^^ These novel interactions regulate the activity of the resultant complexes and may be involved in uPA / uPAR mediated signal transduction . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and plasminogen activator inhibitors ( PAI 1 and PAI 2 ) , all play important roles in tumour invasion and metastasis . ^^^ PATIENTS AND METHODS : The levels of uPA , uPAR PAI 1 and PAI 2 were measured by enzyme linked immunosorbent assay ( ELISA ) in triton extracts , prepared from 88 NSCLC tissues ( stage 1 IIIa ) and 74 normal lung tissues from the same patients . ^^^ RESULTS : The expression levels of uPA , uPAR , PAI 1 and PAI 2 were significantly higher in tumour tissues as compared to their normal equivalents ( all , P < 0 . 0001 ) . ^^^ Significant relations were found between gender and uPA ( P = 0 . 04 ) or uPAR ( P < 0 . 001 ) , and between PAI 2 and pathological stage ( P = 0 . 03 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor ( uPA R or CD 87 ) for the serine protease urokinase type plasminogen activator ( uPA ) plays a central role in invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It has become more and more clear in recent decades that the plasminogen activation system , which includes urokinase type plasminogen activator ( uPA ) , urokinase type plasminogen activator receptor ( uPAR ) , plasminogen activator inhibitor ( PAI ) 1 and PAI 2 , plays a very important role in the aggressiveness of cancer . ^^^ The positive rates of uPA , uPAR , PAI 1 and PAI 2 for immunohistochemical stains in cancer tissues were 78 . 9 , 68 . 4 , 57 . 9 and 31 . 6 % , respectively . ^^^ In ELISA , there were significant differences between cancer and non cancer tissues in concentration of uPA , uPAR and PAI 1 ( P < 0 . 0003 , 0 . 0024 and 0 . 01 , respectively ) , but there was no significant difference in that of PAI 2 ( P = 0 . 37 ) . ^^^ These results suggest that uPA , uPAR and PAI 1 are related to invasion of HCC . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We explored the role of urokinase and tissue type plasminogen activators ( uPA and tPA ) , as well as the uPA receptor ( uPAR ; CD 87 ) in mouse severe malaria ( SM ) , using genetically deficient ( / ) mice . ^^^ The mortality resulting from Plasmodium berghei ANKA infection was delayed in uPA ( / ) and uPAR ( / ) mice but was similar to that of the wild type ( + / + ) in tPA ( / ) mice . ^^^ Parasitemia levels were similar in uPA ( / ) , uPAR ( / ) , and + / + mice . ^^^ SM was associated with a profound thrombocytopenia , which was attenuated in uPA ( / ) and uPAR ( / ) mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we determined if the urokinase type plasminogen activator ( uPA ) and / or the urokinase type plasminogen activator receptor ( uPAR ) were responsible for the invasion activity of a human glioma cell line . ^^^ Northern blot analysis showed that bFCF and TGF alpha treatment was associated with increases in cellular mRNA levels of uPA and uPAR . ^^^ Zymographic activity correlated to mRNA levels of uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Involvement of the [ uPAR : uPA : PAI 1 : LRP ] complex in human myogenic cell motility . ^^^ At the cell surface , receptor ( uPAR ) bound urokinase ( uPA ) binds its inhibitor PAI 1 , localized in the matrix , and the complex is internalized by endocytic receptors , such as the low density lipoprotein receptor related protein ( LRP ) . ^^^ Using a two dimensional motility assay and microcinematography , we showed that any interference with the [ uPAR : uPA : PAI 1 ] complex formation , and interference with LRP binding to this complex , markedly decreased myogenic cell motility . ^^^ Inhibition of cell motility was associated with suppression of both filopodia and membrane ruffling activity . [ uPAR : uPA : PAI 1 : LRP ] complex formation involves high affinity molecular interactions and results in quick internalization of the complex . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Leukocytes express both urokinase type plasminogen activator ( uPA ) and the urokinase receptor ( uPAR , CD 87 ) . ^^^ The requirement for uPAR in neutrophil recruitment is independent of the serine protease uPA , as neutrophil recruitment in uPA / mice is indistinguishable from recruitment in WT mice . uPAR / mice have impaired clearance of P . aeruginosa compared with WT mice , as demonstrated by CFU and comparative histology . ^^^ We conclude that uPAR is required for the recruitment of neutrophils to the lung in response to P . aeruginosa pneumonia and that this requirement is independent of uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Effects of diabetes and hypoxia on gene markers of angiogenesis ( HGF , cMET , uPA and uPAR , TGF alpha , TGF beta , bFGF and Vimentin ) in cultured and transplanted rat islets . ^^^ These factors include hepatocyte growth factor ( HGF ) and its receptor c MET , and urokinase plasminogen activator ( uPA ) and its receptor uPAR , basic fibroblast growth factor ( bFGF ) , TGF alpha and TGF beta 1 . ^^^ Expression of uPA was up at day 3 and remained high ; expression of uPAR was also up at day 3 but then fell to control levels at day 14 . ^^^ In the grafts of diabetic recipients the expression of HGF , uPA and uPAR were delayed , being clearly expressed at day 5 rather than day 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
FACS analyses revealed that the hybrids compete for binding of uPA to the cell surface associated uPA receptor ( uPAR ) expressed on human U 937 cells . ^^^ The measured K ( D ) value of a papain bound cystatin variant harboring the uPAR binding sequence of uPA ( chCys uPA ( 19 31 ) ) and soluble uPAR was 17 nm ( K ( D ) value for uPA / uPAR interaction , 5 nm ) . ^^^ These results indicate that cystatins with a uPAR binding site are efficient inhibitors of cysteine proteases and uPA / uPAR interaction at the same time . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We now report that uPAR cell surface expression can be positively regulated by its ligand , uPA , in thyroid cells . ^^^ Finally , uPA up regulates uPAR expression also in other cell lines of different type and origin , thus suggesting that the regulatory role of uPA on uPAR expression is not restricted to thyroid cells , but it occurs in different tissues , both normal and tumoral . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A high affinity receptor for urokinase type plasminogen activator ( uPAR ) has been identified on the plasma membrane of a number of different cell types , and has been shown to be important for plasminogen activation , cell adhesion , and possibly signal transduction . uPAR and uPA cosediment with secretory vesicles and specific granules by subcellular fractionation and translocate to the plasma membrane upon activation of neutrophils . ^^^ Here the subcellular distribution of uPAR and uPA is studied by electron microscopy of neutrophils using immunogold double labeling for uPAR and uPA and a set of markers for well defined subtypes of granules : matrix metalloproteinase type 9 ( MMP 9 ) for gelatinase granules , lactoferrin ( LF ) for specific granules , and myeloperoxidase ( MPO ) and neutrophil elastase ( NE ) for primary granules . ^^^ With this technique uPAR colocalizes with uPA in 71 % of labeled granules . ^^^ Low levels of co localization were found for uPAR and LF ( 7 % ) and for uPA and lactoferrin ( 5 % ) . ^^^ The results indicate that uPAR and uPA are present in gelatinase granules and primary granules , but rarely in specific granules . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase ( uPA ) to its receptor ( uPAR ; CD 87 ) focuses proteolytic activity on the cell surface and this system is of importance in malignant matrix degradation and tumour invasion . ^^^ By immunocytochemistry and flow cytometry , we found that primary myeloma cells and myeloma cell lines expressed uPA and uPAR . ^^^ In cell lines , uPA and uPAR were located both on the cell surface and intracellularly , but the expression of both proteins was low . ^^^ We conclude that myeloma cells are able to produce uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We studied the expression of uPA , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor type 1 ( PAI 1 ) in human breast carcinomas and their bone metastases , using in situ hybridisation . ^^^ The majority of the tumours examined expressed low to moderate levels of uPA mRNA and low to high levels of uPAR and PAI 1 mRNA , which was predominantly localised to the epithelial tumour cells . ^^^ There was slight over expression of uPA and PAI 1 mRNA and a marked increase in uPAR mRNA expression in the malignant tumours compared with benign tissue . ^^^ Overall , uPAR and PAI 1 mRNA expression was found to be more variable than uPA mRNA , suggesting a possible role of the receptor and inhibitor in the regulation of uPA activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor 1 ( PAI 1 ) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factors such as uPAR and growth factors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Cellular accumulation of uPA PAI 1 [ correction of UPA PAI 1 ] and uPA PAI 2 [ correction of UPA PAI 2 ] complexes in early ( pT 1 ) breast cancer : a new link in the uPA UPAr PAI chain . ^^^ RESULTS : The immunohistochemical reaction with uPA PAI 1 and uPA PAI 2 complexes was cytoplasmic and localized inside the tumor cells , with no , or only minimal reaction in the stromal cells . uPA positivity detected by this method correlated significantly with ER expression ( p = 0 . 031 ) , PR expression ( p = 0 . 030 ) , favorable nuclear grade ( p = 0 . 0087 ) and marginally with a low proliferation rate ( p = 0 . 088 ) , which was the opposite of the results reported by most other groups when studying either free uPA or uPA bound to its membrane receptor ( uPAr ) in similar tumors . ^^^ CONCLUSION : From our results we conclude that uPA PAI 1 and uPA PAI 2 complexes are formed inside the tumor cells for the purpose of inactivating free or uPAr bound uPA , which explains why our findings were the reverse of those obtained when studying these latter forms . ^^^ A model incorporating our data and the present knowledge on the uPA uPAr PAI chain is proposed . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Some neutrophils and monocyte / macrophages in the fibrin layer were immunostained for tPA , uPA , uPAR , and MMP 1 , 2 and 3 . ^^^ Some spindle shaped cells surrounding the graft were immunostained for uPA , uPAR , MMP 1 , 2 , 3 , 7 and 9 , and TIMP 1 and 2 . ^^^ Some multi nucleated giant cells were immunostained for MMP 7 and 9 , tPA , PAI 1 , uPA , and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The role of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in fibrinolysis remains unsettled . ^^^ In contrast , uPA ( / ) and tissue type plasminogen activator tPA ( / ) mice , but not uPAR ( / ) mice , showed a marked impairment in pulmonary fibrinolysis throughout the experimental period . ^^^ The increment in clot lysis was 4 fold greater in uPA ( / ) mice infused with the same concentration of scuPA complexed with soluble recombinant uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OSM stimulated increased mRNA levels of urokinase plasminogen activator ( uPA ) and urokinase plasminogen activator receptor ( uPAR ) in a time and dose dependent manner . ^^^ Transcriptional run off and mRNA stability analysis demonstrated that the increase in uPA and uPAR mRNA levels was due to both increased gene transcription and mRNA stability . ^^^ The increase in mRNA correlated with increased protein levels of both uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) is a potent catalyst of extracellular proteolysis , which also binds to a high affinity plasma membrane receptor ( uPAR ) . ^^^ Transgenic mice overexpressing either uPA or uPAR in basal epidermis and hair follicles had no detectable cutaneous alterations . ^^^ In contrast , bi transgenic mice overexpressing both uPA and uPAR , obtained by crossing the two transgenic lines , developed extensive alopecia induced by involution of hair follicles , epidermal thickening and sub epidermal blisters . ^^^ The phenotype was due to uPA catalytic activity since combined overexpression of uPAR and uPAR binding but catalytically inactive uPA in the same tissue was not detrimental in another bi transgenic line . ^^^ Thus , combined overexpression of uPA and uPAR acts in synergy to promote pathogenic extracellular proteolysis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Selectively aggregating uPA occupied uPAR produced smaller increases in [ Ca2+ ] 1 , but saturating uPAR with HMW uPA increased the response to approximate that of uPAR cross linking . ^^^ By contrast , selectively cross linking uPA occupied uPAR was capable of directly inducing superoxide release as well as enhancing FMLP stimulated superoxide release . ^^^ We conclude that uPAR aggregation initiates activation signaling in polymorphonuclear neutrophils through at least two distinct uPA dependent and uPA independent pathways , increasing their proinflammatory potency ( degranulation and oxidant release ) and altering expression of CD11b / CD18 to favor a firmly adherent phenotype . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator receptor ( uPAR ) binds the urokinase type plasminogen activator ( uPA ) and facilitates a proteolytic cascade focused at the cell surface . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have recently demonstrated that both kinases are associated with the uPA receptor ( uPAR ) and mediate uPA induced activation of signal transducers and activators of transcription ( Stat 1 , Stat 2 , and Stat 4 ) in human vascular smooth muscle cells ( VSMC ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) , and its receptor ( uPAR ; CD 87 ) facilitate cancer cell invasion and metastasis . ^^^ Whereas uPA and PAI 1 antigen levels determined in tumor tissue extracts of breast cancer patients correlate with disease recurrence and overall survival , the prognostic relevance of uPAR is still a matter of debate . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this paper we describe the expression of the tissue plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) and the uPA receptor ( uPAR ) , in normal and atheromatous human vascular tissue obtained at coronary and peripheral vascular surgery . tPA , uPA , PAI 1 and uPAR antigens were localised by immunohistochemistry . ^^^ In normal saphenous vein or internal mammary artery , expression of tPA , uPA and PAI expression is associated with endothelium and with intimal or medial smooth muscle cells , but expression is at a low level . uPAR protein was seen on the endothelium of normal saphenous vein or internal mammary artery but absent on the smooth muscle cells . ^^^ In complex atheroma tPA , uPA , PAI and uPAR proteins were associated with the endothelium , groups of smooth muscle cells ( in the intima and around vascular channels , but not with the media ) , infiltrating mononuclear cells , and also with acellular areas . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , plasminogen ( Plg ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) have been observed in many cancers and may contribute to progression and metastasis . ^^^ In addition , we determined the effect of down regulation of uPAR on the invasive / metastatic capability of CRC cells , by measuring antisense uPAR transfected HCT 116 and control cell lines , in terms of uPAR expression , uPA binding activity , invasiveness through Matrigel in vitro and metastasis after cecal orthotopic implantation in nude mice in vivo . ^^^ We found that higher expression of uPA or uPAR in primary tumor tissues was positively correlated with distant metastasis of CRC ( Mann Whitney , p < 0 . 02 ) and negatively correlated with both patient overall survival ( OS ) and cancer specific survival ( CSS ; Cox model , p < 0 . 04 ) . ^^^ The prognostic value of uPA and uPAR for both OS and CSS was independent of other variables ( multivariate Cox model , p < 0 . 007 ) . ^^^ Antisense uPAR transfected HCT 116 cells , which expressed significantly lower levels of total cellular and cell surface uPAR proteins and uPA binding activity compared with either wild type or cells transfected with vector alone ( Bonferroni , p < 0 . 05 / 3 ) , consistently showed decreased invasiveness through Matrigel ( Bonferroni , p < 0 . 05 / 3 ) and decreased metastasis formation in nude mice ( Fisher , p < 0 . 05 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The generation of the broad specificity serine protease plasmin in the pericellular environment is regulated by binding of the urokinase type plasminogen activator ( uPA ) to its specific glycosylphosphatidylinositol ( GPI ) anchored cell surface receptor , uPAR . ^^^ To further study the role of uPAR in this mechanism , we have expressed two directly membrane anchored chimeric forms of uPA , one anchored by a C terminal GPI moiety ( GPI uPA ) , the other with a C terminal transmembrane peptide ( TM uPA ) . ^^^ In both cell lines , GPI uPA activated cell associated plasminogen with characteristics both qualitatively and quantitatively indistinguishable from those of uPAR bound uPA . ^^^ However , the data also demonstrate that , in the presence of an alternative mechanism for uPA localization , uPAR is dispensable and , therefore , unlikely to participate in any additional interactions that may be necessary for the efficiency of this proteolytic system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Immunohistochemical expression of uPA , uPAR , and PAI 1 in breast carcinoma . ^^^ We have used immunohistochemistry to examine three components of this system , ie , uPA , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) , in a pilot study on 142 cases of breast carcinoma . ^^^ Fibroblastic expression of both uPA and uPAR were positively correlated with tumor size . ^^^ These results suggest that strong expression of uPA , uPAR , and PAI 1 in fibroblasts rather than in tumor cells have the most impact on the clinical behavior of breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To assess the role of urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) on the invasive potential of cancer cells , in vitro experiments were performed using two human gastric cancer cell lines , NUGC 3 and MKN 28 . ^^^ NUGC 3 cells secreted a higher level of uPA than MKN 28 cells , while the uPAR expression of NUGC 3 cells was lower than that of MKN 28 cells . ^^^ These results suggest that uPA promotes the invasive capacity of the uPAR positive cancer cells , and that stromal cells may play an important role in cancer cell invasion by supplying uPA and / or promoting uPA production . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation ( PA ) system , immunohistochemical stainings for activators of plasminogen ( tissue type ( tPA ) and urokinase type ( uPA ) ) , inhibitors of plasminogen activation ( type 1 ( PAI 1 ) and type 2 ( PAI 2 ) ) and the receptor for uPA ( uPAR ) were performed on 214 routinely processed melanoma lesions . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator ( uPA ) to its receptor ( uPAR / CD87 ) regulates cellular adhesion , migration , and tumor cell invasion . ^^^ It has been proposed that uPAR forms cis interactions with integrins as an associated protein and thereby transduces proliferative or migratory signals to cells upon binding of uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To investigate the prognostic significance of the plasminogen activation system in human chondrosarcoma , the immunohistochemical expression of urokinase type plasminogen activator ( uPA ) , urokinase type plasminogen activator receptor ( uPAR ) , plasminogen activator inhibitor , 1 ( PAI 1 ) and 2 ( PAI 2 ) were analyzed in 28 patients with chondrosarcoma . ^^^ These results demonstrated the usefulness of uPA , uPAR and PAI 2 expression as biological prognostic indicator and the importance of the plasminogen activation system in tumor progression and metastasis in chondrosarcoma . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of this study was to determine the level of mRNA expression for the genes encoding urokinase ( uPA ) , urokinase receptor ( uPAR ) , and plasminogen activator inhibitor ( PAI 2 ) in endometrial carcinomas . ^^^ METHODS : In this study , the expression of uPA , uPAR , and PAI 2 mRNA was examined in normal endometrial tissue ( n = 16 ) and endometrial carcinoma tissues ( n = 34 ) by Northern blot analysis . ^^^ The expression of both uPA and uPAR mRNA also increased with each progression in clinical stage . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The activity of MMP 2 is potentiated by binding of uPA to the uPA receptor ( uPAR ) . ^^^ METHODS : The expression of uPA , uPAR , the tissue type plasminogen activator , and plasminogen activator inhibitor ( PAI ) 1 and PAI 2 was investigated using reverse transcription followed by polymerase chain reaction and Western blotting . ^^^ RESULTS : These provided direct evidence of elevated expression of uPA and uPAR at the mRNA and protein levels in venous leg ulcers , in comparison with healthy skin . ^^^ By immunohistochemistry , elevated expression of uPA and uPAR was detected . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study was designed to investigate the relationship of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) to invasion and metastasis of hepatocellular carcinoma ( HCC ) . ^^^ The expression of uPA , uPAR , and PAI 1 in HCC was determined by immunohistochemistry , Northern blot , and an LCI D 20 nude mouse metastatic model of HCC . ^^^ The overexpression of uPA , uPAR , and PAI 1 was found in HCC , especially in the patients with portal cancer embolus , tumor invasion , and metastasis . ^^^ Immunohistochemistry results showed that the rate of positive staining of uPA , uPAR , and PAI 1 were higher in HCC than those in the control groups consisting of cancer adjacent tissue and normal liver tissue . ^^^ In the case of HCC invasion , positive uPA and uPAR were seen in 16 and 19 out of 22 patients , respectively ( P < 0 . 01 and P < 0 . 001 , respectively , as compared with the patients without invasion ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The levels of uPA receptor ( uPAR ) mRNAs were also elevated simultaneously upon HGF / SF stimulation , and the cell surface associated uPA activity was also elevated by the treatment . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study was undertaken to characterize the expression of both uPA and its receptor ( uPAR ) in the eutopic and heterotopic endometrial cells from women with adenomyosis by testing both types of epithelial cells for invasive ability . ^^^ When respective stromal cells were cocultured , the heterotopic epithelial cells exhibited significantly higher invasive ability through Matrigel than did the eutopic epithelial cells . uPAR overexpression in the epithelial cells and high secretion of uPA from the stromal cells may contribute to the invasive phenotype of heterotopic endometrium . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator receptor ( uPAR / CD87 ) together with its ligand , urokinase type plasminogen activator ( uPA ) , constitutes a proteolytic system associated with tissue remodelling and leucocyte infiltration . uPAR is a member of the glycosyl phosphatidyl inositol ( GPI ) anchored protein family . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , and its inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) , are proposed to be prognostic factors in some cancers . ^^^ METHODS : To determine the prognostic value of the urokinase plasminogen activation system , contents of uPA , uPAR , and PAI 1 were measured in extracts of endometrial cancer tissue using ELISAs . uPA , uPAR , and PAI 1 levels were determined in 91 , 54 , and 92 extracts , respectively , and correlated with tumor histology , stage , grade , lymph node involvement , prevalence of metastasis , and recurrence as well as with estrogen ( ER ) , progesterone ( PR ) , epidermal growth factor ( EGFR ) receptor and HER 2 / neu contents . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Among the proteases involved in the tumor invasion process , components of the plasminogen activator system ( plasminogen activator type urokinase uPA , its membrane receptor uPAR and its two inhibitors PAI 1 and PAI 2 ) appear to define high risk patients in primary breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The importance of plasminogen activation , mediated by urokinase ( uPA ) and its receptor ( uPAR ) , is well established in many physiologica and pathological processes , such as in cell migration and tumor cell invasion . ^^^ Recently , additional functions have been described for uPA and uPAR , particularly in cell adhesion and chemotaxis . ^^^ The amounts of uPA and uPAR in various tumor types and in the plasma / serum samples of cancer patients have been shown to correlate with survival prognosis , indicating the relevance of these molecules in malignancy . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This increase in invasion could in turn be abolished by antibodies directed to uPA and uPAR and by the plasmin inhibitors epsilon aminocaproic acid and aprotinin . ^^^ The results provide evidence that the vitronectin receptor can enhance invasion by regulating the uPAR / uPA / plasmin system of proteolysis and implicate PKCbeta as an intermediate in the activation pathway . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We define the expression of urokinase type plasminogen activator ( uPA ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and type 2 ( PAI 2 ) , the receptor for uPA ( uPAR ) and fibrin / fibrinogen in monkey implantation sites . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
AIMS : To plasminogen activator system ( PAS ) consists of the plasminogen activators ( urokinase ( uPA ) and tissue type ( tPA ) plasminogen activators ) , the uPA receptor ( uPAR ) , and the plasminogen activator inhibitors ( PAI 1 and PAI 2 ) . ^^^ CONCLUSION : The involvement of the PAS and VEGF in colorectal cancer appears to be complex . uPA , uPAR , PAI 1 , and VEGF were upregulated in tumour tissue and this correlated with Dukes ' s staging and lymphatic invasion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Considering the established role of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) in invasion , this study was undertaken to explore the role of heregulin beta 1 in regulating uPA and uPAR in breast cancer invasion . ^^^ Heregulin beta 1 stimulated signaling initiated the transcription from uPA and uPAR promoters . ^^^ These results suggest that heregulin beta 1 regulation of breast cancer cell invasion may be mediated in part through the up regulation of uPA and uPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cytoskeletal changes are independent of uPA and activation of the RGD binding activity of integrins but require uPAR binding to vitronectin ( VN ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
After this , the expressions of the components of the plasminogen activator system including urokinase type and tissue type plasminogen activator ( uPA and tPA ) , urokinase receptor ( uPAR ) , and type 1 and type 2 plasminogen activator inhibitor ( PAI 1 and PAI 2 ) in strain 95D and 95C cells were determined by RT PCR and immunohistochemical staining . ^^^ The effects of monoclonal antibodies of uPA , uPAR , and PAI 1 on the invasive potential of strain 95D cell line were also evaluated . ^^^ The high metastatic strain 95D cells expressed higher uPA and uPAR and lower tPA and PAI 2 than the low metastatic strain 95C cells . ^^^ Monoclonal antibodies of uPA and uPAR greatly reduced the invasive potential of strain 95D cells in vitro . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
ERK phosphorylation was not induced by tissue type plasminogen activator PAI 1 complex or by uPA PAI 1 complex in the presence of antibodies that block uPA binding to uPAR . uPA PAI 1 complex induced tyrosine phosphorylation of focal adhesion kinase and Shc and sustained association of Sos with Shc , whereas uPA caused transient association of Sos with Shc . ^^^ The kinetics of ERK phosphorylation in response to uPAR ligation determine the function of uPA and uPA PAI 1 complex as growth promoters . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator receptor ( uPAR ) binds pro urokinase plasminogen activator ( pro uPA ) and thereby localizes it near plasminogen , causing the generation of active uPA and plasmin on the cell surface . uPAR and uPA are overexpressed in a variety of human tumors and tumor cell lines , and expression of uPAR and uPA is highly correlated to tumor invasion and metastasis . ^^^ These uPA targeted PrAg proteins were activated selectively on the surface of uPAR expressing tumor cells in the presence of pro uPA and plasminogen . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using Northern blot analysis we have measured the co expression of the matrix metalloprotease MMP 9 , plasminogen activator urokinase type ( uPA ) and its receptor ( uPAR ) mRNAs in 81 biopsies of breast carcinomas with the objective of analyzing the impact of these factors on the overall survival probability of the patients ( median follow up time : 4 years ) . ^^^ Individual mRNA levels of either uPA or uPAR showed parallel variations with MMP 9 mRNA , suggesting a coordinate transcription of these markers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitor ( PAI 1 ) . ^^^ We analyzed the mRNAs for urokinase plasminogen activator ( uPA ) , its receptor ( uPAR ) , and inhibitor ( PAI 1 ) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts . ^^^ The number of mRNA expressing cells for uPA , uPAR and PAI 1 were all significantly increased in solid as compared with cystic malignant tumors . ^^^ In addition , the tumor tissue content of uPA , uPAR and PAI 1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors . ^^^ Increased expression of uPA , uPAR and PAI 1 genes in the solid tumors suggest a correlation with a more aggressive phenotype . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) act in concert to mediate pericellular proteolysis and to stimulate intracellular signalling responsible for cell migration and proliferation . uPA is composed of three domains , a proteolytic domain ( PD ) , a kringle domain ( KD ) and a growth factor like domain ( GFD ) , the last of which mediates the interaction with uPAR . ^^^ Using recombinant forms of uPA , we show that a uPA variant lacking the GFD ( r uPADeltaGFD ) and unable to associate with uPAR is rapidly cleared from the cell surface . ^^^ Soluble uPAR protects uPA from cleavage by plasmin that results in the elimination of GFD , suggesting that uPAR might protect cell bound urokinase from plasmin mediated cleavage between the GFD and KD and subsequent degradation . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This paper describes the detection of CD 44 variant sequences , urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) by immunoluminescence and activity measurements . ^^^ The expression of CD 44 ( v 5 ) , uPA and uPAR on the cell surface was shown by indirect labelling with monoclonal antibodies ( mAb ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : Urinary type plasminogen activator ( uPA ) binding to uPA receptor ( uPAR ) promotes the activation of matrix metalloproteinase 9 ( MMP 9 ) , which degrades amyloid beta protein ( Abeta ) in vitro . ^^^ We investigated the expression of MMP 9 , uPA , and uPAR in post mortem brains from patients with Alzheimer ' s disease ( AD ) and those with vascular dementia ( VD ) . ^^^ The anti MMP 9 antibody , anti uPA antibody , and anti uPAR antibody were used to perform immunohistological analysis . ^^^ RESULTS : In the brain tissues from the AD patients , we found expression of MMP 9 in the cytoplasm of neurons , neurofibrillary tangles , senile plaques , vascular walls and uPAR expression in the cytoplasm of neurons and vascular walls . uPA was detected only in the vascular walls . ^^^ On the other hand , we could not find expression of MMP 9 , uPAR and uPA in the brain tissues of the VD patients , except for the vascular walls . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of the urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) correlates with tumour cell invasiveness and helps to determine the prognosis of prostate and other cancers . ^^^ The purpose of this study was to establish in prostate cancer , the ets family and AP 1 complex transcription factors that might activate the inducible AP 1 and AP 1 / PEA3 elements of the uPA enhancer . uPA and uPAR were expressed preferentially in adenocarcinoma cells , but not the stroma of high grade prostate cancers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A remarkable property of the uPA uPAR system is a pronounced species specificity in ligand recognition . ^^^ Thus , a well described competitive peptide antagonist directed against the human uPAR reacts with only one of the monkey receptors ( chimpanzee uPAR ) , in spite of the fact that uPAR from all of the four species cross reacts with human uPA . ^^^ These findings aid the elucidation of the structure / function relationship of uPAR and , unexpectedly , identify a structural distinction governing the binding of uPA and a very similar peptide antagonist . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Cancer tissues from 71 colorectal cancer patients were assayed quantitatively for antigen levels of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 and 2 ( PAI 1 , PAI 2 ) , and were also assayed immunohistochemically for expression of VEGF protein . ^^^ Among the PA system factors , the uPAR levels were significantly higher in tumors with VEGF overexpression and a multivariate analysis revealed that high uPA level and VEGF overexpression were independent risk factors for liver metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
RESULTS : Nave mice intracorneally infected with P . aeruginosa showed a temporally enhanced expression of tissue type plasminogen activator ( tPA ) , urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) , over a several day holding period . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition , these proteolytic cascades process and release various growth and differentiation factors that are sequestered on the cell surface or within the ECM , which contribute to the evolution of a migratory or invasive cell phenotype . uPA is also able to modulate signaling and cell adhesion through its specific cell surface receptor , uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of urokinase type plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) , critical components of the urokinase plasminogen activator ( uPA ) system , was lower and delayed in IL 6 / livers . ^^^ Despite the fact that active uPAR / uPA complex is critical for hepatocyte growth factor ( HGF ) activation , no differences were detected between the IL 6 + / + and / livers in HGF activation as measured by receptor phosphorylation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Recent evidence suggests that in addition to uPA , its specific cell surface receptor ( uPAR ) may also be a suitable target for the design and development of cancer therapeutic and diagnostic agents . uPAR is central to several pathways implicated in tumor progression and angiogenesis . ^^^ The binding of the uPA zymogen ( scuPA ) to uPAR appears to be a pre requisite for efficient cell surface activation of scuPA to the active two chain form ( tcuPA ) by plasmin , and simple ligand occupancy of uPAR by scuPA initiates various signaling pathways leading to alterations in cell motility and adhesion . ^^^ In addition , other approaches to the modulation of the activity of this system that may also be useful include blocking the interaction of uPAR with integrins and extracellular matrix proteins as well as strategies to down regulate the expression of uPA and uPAR in target cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The role of the urokinase type plasminogen activator ( uPA ) and its receptor ( CD 87 ) in lipodermatosclerosis . ^^^ METHODS : The expression and the functional state of the urokinase type plasminogen activator ( uPA ) , the tissue type plasminogen activator ( tPA ) , the urokinase receptor ( CD 87 ) , the plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) were assayed using reverse transcription polymerase chain reaction , Western blot , fibrin zymography and immunohistochemistry analyses in tissue samples of lipodermatosclerosis . ^^^ RESULTS : Our results provide direct evidence of elevated expression of uPA ( p < 0 . 01 ) and CD 87 ( p < 0 . 01 ) mRNA and protein level in lipodermatosclerosis in comparison with healthy skin . ^^^ By immunohistochemistry , elevated expression of uPA and CD 87 could be detected . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The number of sensory neurons expressing urokinase PA receptor ( uPAR ) mRNA levels increased above sham levels by 8 hr after crush , whereas the number of sensory neurons expressing uPA and tissue PA ( tPA ) mRNAs was significantly increased by 3 d after crush . ^^^ PA mRNA levels were also increased at the crush site , with uPA mRNA elevated by 8 hr after crush and tPA and uPAR mRNA levels markedly increased by 7 d . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We therefore studied the expression of UPA , UPAR , IGF2R , ALK 5 ( TGFBR 1 ) , TGFBR 2 , TGFBR 3 , ENG , ALK 1 , TGFB 1 , TGFB 2 , and TGFB 3 in a series of 14 pancreatic carcinoma cell lines . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Focusing of urokinase type plasminogen activator ( uPA ) to the cell surface via binding to its specific receptor ( uPAR , CD 87 ) is critical for tumor invasion and metastasis . ^^^ Consequently , the inhibition of uPA uPAR interaction on the cell surface might be a promising anti invasion and anti metastasis strategy . ^^^ First , a highly metastatic human lung giant cell carcinoma cell line ( PG ) , used as the target cell for evaluation of this effect , was demonstrated to express both uPA and uPAR . ^^^ Then , ATF , which contains an intact uPAR binding site but is catalytically inactive , was designed as an antagonist of uPA uPAR interaction and was transfected into PG cells . [ ( 3 ) H ] Thymidine incorporation and cell growth curves indicated that expressed ATF did not affect the proliferation of transfected cells . ^^^ In summary , autocrine ATF could act as an antagonist of uPA uPAR interaction , and ATF cDNA transfection could efficiently inhibit the invasion and metastasis of the cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We examined the importance of uPA , its receptor , uPAR , and its inhibitor , PAI 1 , in our in vivo model of metastatic osteosarcoma . ^^^ In the tibial tumors , uPAR mRNA was expressed early ( 4 days ) , whereas uPA and PAI 1 mRNA increased as the tumor invaded the surrounding tissue ( 3 weeks ) . ^^^ Our results suggest that the uPA system plays a role in the local aggressiveness and metastasis of osteosarcoma and , in particular , indicates a possible therapeutic role for uPAR antagonists in the treatment of osteosarcoma . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
On the surface of certain cells , uPARAP forms a ternary complex with the pro form of the urokinase type plasminogen activator ( uPA ) and its primary receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We showed previously that pemphigus IgG enhanced both the activity of urokinase plasminogen activator ( uPA ) in cultured cells and the expression of its receptor ( uPAR ) on uPA binding keratinocytes . ^^^ In the present study , to clarify whether uPAR and uPA activated plasmin are actually involved in the blistering process after pemphigus IgG binding to the cell surface , we examined the effects of the following on uPAR expression and on cell cell detachment in DJM 1 cells , a squamous cell carcinoma line : ( 1 ) phosphatidylinositol specific phospholipase C ( PI PLC ) which releases uPAR from the membrane surface into the culture medium by cleaving the glycosylphosphatidylinositol anchor thus inhibiting uPAR activity , and ( 2 ) uPA inhibitors ( tranexamic acid , aprotinin , p aminobenzonic acid and dexamethasone ) . ^^^ Although uPAR expression on the pemphigus IgG bound cell surface and uPA activation may contribute significantly to the pathogenesis of acantholysis in pemphigus , the mechanisms are complicated and should be defined further . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Significance of the uPA / uPAR system for development of arteriosclerosis and restenosis ] . ^^^ One of the phenotypic changes induced in migrating cells is the increased expression of urokinase plasminogen activator ( uPA ) and of its specific receptor uPAR . ^^^ Both uPA and uPAR are key mediators of extracellular proteolysis . ^^^ UPA / uPAR are multifunctional proteins influencing a great variety of signal transduction pathways ultimately culminating in the regulation of cell migration and proliferation . ^^^ Interaction with the uPA / uPAR system or components of its specific signal transduction pathways may serve as a guide for the development of effective therapeutic strategies to prevent arteriosclerosis and restenosis after percutaneous arterial angioplastic interventions . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Herein we provide evidence for the production by natural killer ( NK ) cells of both uPA and its receptor ( uPAR ) . ^^^ MATERIALS AND METHODS : Western blot analysis , RTPCR , casein / plasminogen zymography , and fluorescence microscopy were employed to detect uPA and uPAR on NK cells . ^^^ RESULTS : NK cell uPA appeared at its characteristic molecular weights , is enzymatically active in casein / plasminogen zymography , and is recognized by monoclonal antibodies . uPAR was detected by RTPCR and fluorescence microscopy . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The interaction between urokinase plasminogen activator ( uPA ) and its cellular receptor ( uPAR ) is a key event in cell surface associated plasminogen activation , relevant for cell migration and invasion . ^^^ In order to define receptor recognition sites for uPA , we have expressed uPAR fragments as fusion products with the minor coat protein on the surface of M 13 bacteriophages . ^^^ Sequence analysis of cDNA fragments encoding uPA binding peptides indicated the existence of a composite uPA binding structure including all three uPAR domains . ^^^ Four regions within the uPAR sequence were found to directly bind to uPA : two distinct regions containing amino acids 13 20 and amino acids 74 84 of the uPAR domain 1 , and regions in the putative loop 3 of the domains 2 and 3 . ^^^ All the uPA binding fragments from the three domains were shown to have an agonistic effect on uPA binding to immobilized uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Focussing of the serine protease urokinase ( uPA ) to the tumor cell surface via interaction with its receptor ( uPAR ) is an important step in tumor invasion and metastasis . ^^^ High level synthesis of recombinant suPAR ( without altering the physiological expression levels of GPI uPAR and uPA in these cells ) resulted in a significant reduction of tumor burden ( up to 86 % ) in the xenogeneic mouse model . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its cell surface receptor ( uPAR ) regulate cellular functions linked to adhesion and migration and contribute to pericellular proteolysis in tissue remodelling processes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase ( uPA ) has the striking ability to cleave its receptor , uPAR , thereby inactivating the binding potential of this molecule . ^^^ Purified full length GPI anchored uPAR ( GPI uPAR ) proved much more susceptible to uPA mediated cleavage than recombinant truncated soluble uPAR ( suPAR ) , which lacks the glycolipid anchor . ^^^ In accordance with this model , when the hydrophobic lipid moiety was removed from the glycolipid anchor by phospholipase C , low concentrations of uPA could no longer cleave the modified GPI uPAR and the reactivity to the peptide antibody was greatly decreased . ^^^ Naturally occurring suPAR , purified from plasma , was found to have a similar resistance to uPA cleavage as phospholipase C treated GPI uPAR and recombinant suPAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , adhesion to vitronectin and fibronectin was reduced by compounds that interfere with integrin function , such as EDTA , anti integrin antibodies , or by antibodies that interfere with the binding of pro uPA to uPAR , soluble uPAR , soluble vitronectin , phosphatidylinositol specific phospholipase C , as well as plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PAI 1 ( plasminogen activator inhibitor 1 ) binds the urokinase type plasminogen activator ( uPA ) and causes its degradation via its receptor uPAR and low density lipoprotein receptor related protein ( LRP ) . ^^^ The inhibitory effect of PAI 1 on uPA dependent chemotaxis is reversed when uPAR internalization is inhibited by the 39 kDa receptor associated protein or by anti LRP antibodies . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Highly significant quantitative increases in urokinase PA ( uPA ) , urokinase receptor ( uPAR ) and plasminogen activator inhibitor 1 were detected in acute multiple sclerosis lesions ( P < 0 . 0001 ) and in uPAR in normal appearing white matter ( P < 0 . 0001 ) compared with control tissue . ^^^ The uPA uPAR complex , concentrated on inflammatory cells in the perivascular zone of the evolving lesion , may facilitate cellular infiltration into the CNS which is amplified by MMP mediated degradation of blood vessel matrix . tPA localization on injured axons may be a marker of axonal damage or represent a protective mechanism aimed at removal of fibrin deposits and restoration of axonal function . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The high affinity interaction between urokinase type plasminogen activator ( uPA ) and its glycolipid anchored receptor ( uPAR ) plays an important role in pericellular plasminogen activation . ^^^ Since proteolytic degradation of the extracellular matrix has an established role in tumor invasion and metastasis , the uPA uPAR interaction represents a potential target for therapeutic intervention . ^^^ By affinity maturation using combinatorial chemistry we have now developed and characterized a 9 mer , linear peptide antagonist of the uPA uPAR interaction demonstrating specific , high affinity binding to human uPAR ( K ( d ) approximately 0 . 4 nM ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) binds to the uPA receptor ( uPAR ) and activates the Ras extracellular signal regulated kinase ( ERK ) signaling pathway in many different cell types . ^^^ When these cells were cultured in the presence of antibodies that block the binding of uPA to uPAR , the level of phosphorylated ERK decreased substantially . ^^^ The mitogen activated protein kinase kinase inhibitor , PD 098059 , decreased expression of uPA and uPAR in MDA MB 231 cells . ^^^ Thus , uPA and the uPAR ERK signaling pathway form a positive feedback loop in these cells . ^^^ When this feedback loop was disrupted with uPA or uPAR specific antibody , uPA mRNA specific antisense oligodeoxynucleotides or PD 098059 , cell growth was inhibited and apoptosis was promoted , as determined by the increase in cytoplasmic nucleosomes and caspase 3 activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Indeed in several tumour types , elevated levels of uPA , its receptor ( uPAR ) or its inhibitor plasminogen activator inhibitor 1 ( PAI 1 ) is associated with a poorer prognosis . ^^^ The aims were to assess whether the uPA , uPAR and / or PAI 1 correlates with angiogenic activity and could therefore be a useful objective clinical measure of tumour neovascularization ; and to clarify whether the poor outcome associated with high levels of the urokinase system is due to its association with angiogenesis . ^^^ The cytosolic levels of uPA , PAI 1 and uPAR were therefore measured by enzyme linked immunoabsorbent assay , together with tumour vascularity , in 136 well characterized invasive breast carcinomas . ^^^ There were significant relationships between uPA and uPAR ( Spearman r=0 . 37 , p < 0 . 0001 ) , uPA and PAI 1 ( Spearman r=0 . 19 , p=0 . 03 ) and between uPAR and PAI 1 ( Spearman r=0 . 23 p=0 . 01 ) . ^^^ A significant correlation was also observed between PAI 1 and vessel remodelling ( Spearman r=0 . 34 , p=0 . 04 ) , patient age ( p=0 . 01 ) , nodal status ( p=0 . 047 ) and tumour grade ( p=0 . 04 ) , but no association between tumour vascularity and PAI ( p=0 . 96 ) , uPA ( p=0 . 69 ) or uPAR ( p=0 . 81 ) was present . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Cyclo 19 , 31 [ D Cys 19 ] uPA 19 31 is a potent competitive antagonist of the interaction of urokinase type plasminogen activator with its receptor ( CD 87 ) . ^^^ Urokinase type plasminogen activator ( uPA ) represents a central molecule in pericellular proteolysis and is implicated in a variety of physiological and pathophysiological processes such as tissue remodelling , wound healing , tumor invasion , and metastasis . uPA binds with high affinity to a specific cell surface receptor , uPAR ( CD 87 ) , via a well defined sequence within the N terminal region of uPA ( uPA 19 31 ) . ^^^ Due to its fundamental role in these processes , the uPA / uPAR system has emerged as a novel target for tumor therapy . ^^^ Previously , we have identified a synthetic , cyclic , uPA derived peptide , cyclo 19 , 31uPA19 31 , as a lead structure for the development of low molecular weight uPA analogues , capable of blocking uPA / uPAR interaction [ Burgle et al . , Biol . ^^^ This led to the identification of cyclo 19 , 31 [ D Cys 19 ] uPA 19 31 as a potent inhibitor of uPA / uPAR interaction , displaying only a 20 to 40 fold lower binding capacity as compared to the naturally occurring uPAR ligands uPA and its amino terminal fragment . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase receptor ( uPAR ) is linked to cellular migration through its capacity to promote pericellular proteolysis , regulate integrin function , and mediate cell signaling in response to urokinase ( uPA ) binding . ^^^ Here we show that a major beta 1 integrin partner for uPAR / uPA signaling is alpha 3 . ^^^ Soluble uPAR bound to recombinant alpha3beta1 in a uPA dependent manner ( K ( d ) < 20 nM ) and binding was blocked by a 17 mer alpha3beta1 integrin peptide ( alpha 325 ) homologous to the CD11b uPAR binding site . uPAR colocalized with alpha3beta1 in MDA MB 231 cells and uPA ( 1 nM ) enhanced spreading and focal adhesion kinase phosphorylation on fibronectin ( Fn ) or collagen type 1 ( Col ) in a pertussis toxin and alpha 325 sensitive manner . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have demonstrated that certain aggressive breast cancer cell lines , which have highly activated endogenous urokinase type plasminogen activator ( uPA ) uPA receptor ( uPAR ) systems , do not express high levels of cell surface K 8 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The requirement for urokinase plasminogen activator ( uPA ) and uPA receptor ( uPAR ) in T lymphocyte migration is unknown . uPA ( / ) mice have fewer pulmonary lymphocytes in response to certain infections , but its unknown whether this is due to diminished recruitment . ^^^ Three days later , fluorescently labeled lymphoblasts from background matched control wild type ( WT ) , uPA ( / ) , or uPAR ( / ) donor mice were injected i . v . , and their recruitment was determined . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present study we examined the relation of uPA ( urokinase plasminogen activator ) , uPAR ( uPA receptor ) and PAI 1 ( plasminogen activator inhibitor type 1 ) to the biological growth behavior of esophageal cancer , as well as their influence on survival in esophageal cancer . ^^^ MATERIALS and METHODS : The expression and distribution of uPA , uPAR and PAI 1 were analyzed by Northern blot analysis and immunostaining in 41 resected esophageal cancers and in normal esophagi . ^^^ RESULTS : Northern blot analysis revealed a 5 . 0 , 3 . 6 and 5 . 4 fold increase in uPA , uPAR , and PAI 1 mRNA levels in esophageal cancer , respectively , in comparison to normal controls ( p < 0 . 01 ) . ^^^ Statistical analysis revealed no differences in uPA , uPAR and PAI 1 immunoreactivity between well differentiated , moderately differentiated and poorly differentiated tumors . ^^^ Furthermore , survival analysis showed no difference in patients whose tumors exhibited positive uPA and uPAR immunostaining ( median 11 months , range 4 36 months ) versus patients whose tumors exhibited negative uPA and uPAR immunostaining ( median 11 months , range 3 51 months ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
There is abundant evidence that the plasminogen activator ( PA ) system with its key components uPA ( urokinase type plasminogen activator ) , its cell surface receptor uPA R ( CD 87 ) and its inhibitor PAI 1 plays a key role in tumour invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
There is ample information on the clinical role of biologic factors in female breast cancer : urokinase type plasminogen activator ( uPA ) , its receptor uPAR , its inhibitors PAI 1 and PAI 2 , cathepsin D and pS 2 protein . ^^^ We determined the cytosolic levels of oestrogen receptor ( ER ) , progesterone receptor ( PgR ) , cathepsin D , pS 2 protein , uPA , uPAR , PAI 1 and PAI 2 of the primary tumour tissues from 40 male breast cancer patients . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have recently reported that the urokinase type plasminogen activator ( uPA ) up regulates the cell surface expression of its own receptor ( uPAR ) in several cell types , independently of its enzymatic activity . uPA has no effect on kidney 293 cells which do not express uPAR and then can not bind uPA . ^^^ Kidney cells , transfected with the coding region of uPAR cDNA , express very large amounts of uPAR and respond to uPA stimulation by regulating uPAR both at mRNA and protein levels . uPA effect occurs also in the presence of the transcriptional inhibitor dichloro ribobenzimidazole , whereas it is abolished by the protein synthesis inhibitor cycloheximide . ^^^ Moreover , uPA dependent uPAR up regulation correlates with the increase of a complex between the coding region of uPAR mRNA and an unknown cellular factor . ^^^ We then propose that uPA regulates uPAR expression at a post transcriptional level , by promoting the binding of uPAR mRNA to a stabilizing factor . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) plays a role in destruction of joint tissue in rapidly destructive coxarthropathy ( RDC ) ] . ^^^ To examine the relationship between the angiogenesis and bone destruction , expression of urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) , which are necessary for angiogenesis was histochemically investigated . ^^^ Immunohistochemical staining was performed on paraffin sections , using monoclonal antibodies against human uPA and uPAR . ^^^ RESULT : There was a difference between expression of uPA and that of uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We used three recombinant ( r ) forms of uPA , which differ markedly in their proteolytic activities and abilities to bind to the uPA receptor ( uPAR ) , to determine , which property most influences the healing responses of balloon catheter injured rat carotid arteries . ^^^ After injury , uPA and uPAR expression increased markedly throughout the period when medial SMCs were rapidly proliferating and migrating to form the neointima . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present study was undertaken to investigate the expression of the molecules of the PA system ( tPA , uPA , PAI 1 , uPAR , LRP ) , as well as several members of the MMP family and their inhibitors in the course of actively induced EAE in BALB / c mice . ^^^ Inflammatory cells expressed uPA receptor , uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Thrombin / antithrombin 3 complex ( TAT ) , soluble fibrin ( SF ) , total fibrinogen and fibrin degradation products ( TDP ) , plasminogen activator inhibitor type 1 ( PAI 1 ) , urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) were measured preoperatively , starting anesthesia , during surgery and postoperatively . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Treatment with receptor associated protein ( RAP ) , a specific inhibitor of low density lipoprotein receptor related protein , lead to a significantly increased level of secreted uPA and cell surface uPAR in maspin transfectants but not in the mock control cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase ( uPA ) and urokinase receptor ( uPAR ) dependent cell adhesion to the extracellular matrix protein vitronectin ( Vn ) is an important event in wound healing , tissue remodeling , immune response , and cancer . ^^^ We recently demonstrated that in human vascular smooth muscle cells ( VSMC ) uPA / uPAR are functionally associated with the ectoprotein kinase casein kinase 2 ( CK 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase type plasminogen activator ( uPA ) to its receptor ( uPAR ) in various cell types has been proposed as an important feature of many cellular processes requiring extracellular proteolysis , cell adhesion , motility , and invasion . uPAR attaches to the cell surface with a glycosylphophatidylinositol ( GPI ) anchor , and serves to localize and accelerate the proteolysis cascade . ^^^ In this study , we examined both uPA and uPAR levels in human gingival fibroblasts treated with an inflammatory cytokine , interleukin 1beta ( IL 1beta ) . ^^^ In addition , IL 1beta increased the protein and mRNA levels of both uPA and uPAR in gingival fibroblasts . ^^^ These findings suggest that the enhancement of uPA and uPAR levels by IL 1beta may play an important role in the progression of periodontal diseases through pericellular proteolysis , and subsequent cellular behavior . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) system is responsible for invasion through uPA enzymatic activity and for migration through the binding of uPA to the uPA receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) system is a dynamic complex in which the membrane receptor uPAR binds uPA that binds the plasminogen activator inhibitor ( PAI ) 1 localized in the extracellular matrix , resulting in endocytosis of the whole complex by the low density lipoprotein receptor related protein ( LRP ) . ^^^ We previously reported a nonproteolytic role of the [ uPAR : uPA : PAI 1 : LRP ] complex operative in cell migration . ^^^ We showed that the uPA system and LRP are localized at filopodia of invasive cells , and that formation / internalization of the [ uPAR : uPA : PAI 1 : LRP ] complex is required for attachment and migration of cancer cells on plastic and on a PAI 1 coat . ^^^ Migration velocity , expression of the uPA system , use of the [ uPAR : uPA : PAI 1 : LRP ] complex to migrate , and promigratory effects of PAI 1 paralleled cancer cell invasiveness . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasma membrane urokinase plasminogen activator receptor ( uPAR ) localizes and enhances activation of pro uPA . ^^^ Active uPA , in turn , promotes increased degradation of the extracellular matrix ( ECM ) by activation of plasminogen . uPAR binds to ECM molecules and integrins , which can affect cellular adhesion , signal transduction , and gene regulation . ^^^ In addition , the function of uPAR bound uPA during in vitro prostatic development was studied by adding recombinant peptide competitive inhibitors of uPA uPAR binding . ^^^ These observations suggest that disruption of uPA binding to uPAR results in a retardation of the development of newborn VPs . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Antibodies to both uPA and uPA receptor ( uPAR ) were shown to significantly inhibit cell invasion , as did the uPA inhibitors ( plasminogen activator inhibitor 1 [ PAI 1 ] , p aminobenzamidine [ PABN ] , aprotinin , and amiloride ) . ^^^ Both anti uPA and anti uPAR antibodies inhibited invasion to a level comparable to that of the control vector transfected cells . ^^^ Cell migration experiments performed with the parental cell lines in the presence or absence of anti uPA or anti uPAR antibodies showed that uPA is also required for migratory responsiveness to exogenous OPN . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The single deficiency of tPA , uPA , or uPAR , as well as combined deficiencies of uPA and tPA , did not dramatically affect microvessel formation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We now show that FPRL1 / LXA4R , a G protein coupled receptor for a number of polypeptides and for the endogenous lipoxin A 4 ( LXA 4 ) , is the link between urokinase type plasminogen activator ( uPA ) and migration as it directly interacts with an activated , soluble , cleaved form of uPA receptor ( uPAR ) ( D2D3 ( 88 274 ) ) to induce chemotaxis . ^^^ In this article we show that ( 1 ) both uPAR and FPRL1 / LXA4R are necessary for the chemotactic activity of uPA whereas FPRL1 / LXA4R is sufficient to mediate D2D3 ( 88 274 ) induced cell migration . ( 2 ) Inhibition or desensitization of FPRL1 / LXA4R by antibodies or specific ligands specifically prevents chemotaxis induced by D2D3 ( 88 274 ) in THP 1 cells and human peripheral blood monocytes . ( 3 ) Desensitization of FPRL1 / LXA4R prevents the activation of tyrosine kinase Hck induced by D2D3 ( 88 274 ) . ( 4 ) D2D3 ( 88 274 ) directly binds to FPRL1 / LXA4R and is competed by two specific FPRL1 / LXA4R agonists , the synthetic MMK 1 peptide and a stable analog of LXA 4 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
When negative PAI 1 conupared with positive urokinase type plasminogen activator ( uPA ) and positive uPA receptor ( uPAR ) . ^^^ The nambeigs invasion case increased , the difference was more significant than that in the group with negative PAI 1 , uPA and uPAR ( P = 0 . 039 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The AGS gastric cancer cell line , which has urokinase type plasminogen activator receptor ( uPAR ) but lacks uPA , was transfected with a plasmid containing human uPA cDNA and injected into the backs of SCID mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) uPA receptor ( uPAR ) and epidermal growth factor ( EGF ) EGF receptor ( EGFR ) expression is highly correlated with breast cancer metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
IL 2 mediated upregulation of uPA and uPAR in natural killer cells . ^^^ Urokinase plasminogen activator ( uPA ) and its receptor uPAR play a major role in immune cell mediated , including natural killer ( NK ) cell mediated , degradation of extracellular matrices . ^^^ Herein , we investigate the effects of IL 2 on NK cell uPA and uPAR . ^^^ RNA and protein analyses showed upregulation of uPA and uPAR following IL 2 stimulation . ^^^ Gel shift assays and Western blots detected uPA and uPAR mRNA binding proteins ( mRNABPs ) , previously shown to destabilize uPA and uPAR mRNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We investigated the role of uPAR and urokinase plasminogen activator ( uPA ) during pneumonia caused by a beta ( 2 ) integrin independent respiratory pathogen , Streptococcus pneumoniae . uPAR deficient ( uPAR ( / ) ) , uPA deficient ( uPA ( / ) ) , and wild type ( Wt ) mice were intranasally inoculated with 10 ( 5 ) CFU S . pneumoniae . uPAR ( / ) mice showed reduced granulocyte accumulation in alveoli and lungs when compared with Wt mice , which was associated with more S . pneumoniae CFU in lungs , enhanced dissemination of the infection , and a reduced survival . ^^^ This function is even more pronounced when uPAR is unoccupied by uPA . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We took advantage of genetically deficient mice to explore the role of urokinase ( uPA ) and tissue type ( tPA ) PAs , as well as the uPA receptor ( uPAR , CD 87 ) in platelet kinetics . ^^^ RESULTS : Platelets counts were within the same range in wild type ( + / + ) , uPA , tPA and uPAR deficient mice . ^^^ Platelet survival was similar in + / + , uPA / , tPA / but markedly reduced in uPAR / mice . ^^^ CONCLUSION : These results demonstrate that uPAR , but not uPA or tPA , is essential for maintaining normal platelet survival . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and the uPA receptor ( uPAR ) are key components in the plasminogen activation system , serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion . ^^^ We recently described a new uPAR associated protein ( uPARAP ) , an internalization receptor that interacts with the pro uPA : uPAR complex . ^^^ We suggest that uPARAP is involved in the clearance of the uPA : uPAR complex as well as other possible ligands during benign and malignant tissue remodeling . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The increase of VSMC migration in coculture was equivalent to the uPA induced migration of monocultured VSMC and was blocked by addition into coculture of soluble uPAR ( suPAR ) . ^^^ Analysis of uPA and uPAR expression in cocultured cells demonstrated that monocytes are a major source of uPA , whose expression increases in coculture five fold , whereas VSMC display an increased expression of cell surface associated uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The serine protease urinary plasminogen activator or urokinase ( uPA ) , produced in abundance by many malignancies , plays a key role in tumor cell invasion and metastasis . uPA is localized within the malignant cell milieu via its cell surface receptor [ uPA receptor ( uPAR ) ] , which is expressed by tumor and tumor associated cells . ^^^ Together , these studies demonstrate the ability of anti uPAR antibody to decrease tumor volume and detect the presence of microscopic occult tumor metastases in malignancies where uPA / uPAR play a key role in tumor progression . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Anti urokinase type plasminogen activator ( uPA ) and anti uPAR antibodies reduced the migration and invasion activities of R 1 and R 2 cells to baseline levels . ^^^ CONCLUSIONS : Overexpression of LR 11 induces enhanced migration and invasion activities of intimal SMCs in vitro , probably through its regulation of the uPA / uPAR system . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In contrast , neither plasmin generation nor binding of UPA to its receptor ( CD 87 ) were required for UPA mediated mitogenic effects . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) receptor ( uPAR ) is expressed on the surface of glioblastoma and some other tumor cells and endothelial cells . ^^^ We synthesized a recombinant fusion protein , DTAT , which contains the catalytic portion of diphtheria toxin ( DT ) for cell killing fused to the noninternalizing amino terminal ( AT ) fragment of uPA , and investigated its effectiveness in targeting uPAR positive tumor cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The components of the PPS include the urokinase plasminogen activator ( uPA ) , its cell surface receptor urokinase plasminogen activator receptor ( uPAR ) , and its naturally occurring inhibitors , plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) . ^^^ Increases in tumor and serum levels of uPA , uPAR , and PAI 1 are associated with a worse prognosis in patients with colon cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using flow cytometry and whole cell binding of radiolabelled uPA , we found a high level of uPA receptor ( uPAR ) expression in granulocytes ( 3 . 9 10 104 + / 0 . 9 10 104 sites / cell ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study examined the effect of the preovulatory gonadotropin surge on the temporal and spatial regulation of tissue plasminogen activator ( tPA ) , urokinase plasminogen activator ( uPA ) , and uPA receptor ( uPAR ) mRNA expression and tPA , uPA , and plasmin activity in bovine preovulatory follicles and new corpora lutea collected at approximately 0 , 6 , 12 , 18 , 24 , and 48 h after a GnRH induced gonadotropin surge . ^^^ Messenger RNAs for tPA , uPA , and uPAR were increased in a temporally specific fashion within 24 h of the gonadotropin surge . ^^^ Localization of tPA mRNA was primarily to the granulosal layer , whereas both uPA and uPAR mRNAs were detected in both the granulosal and thecal layers and adjacent ovarian stroma . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Adhesion is reversed when the uPA enzyme is captured by its receptor ( uPAR ) , causing uPAR to bind to CD11b at a second site ( residues 424 440 ) that is in between the N terminal 1 domain and the divalent cation binding region . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Integrity of the three domain structure of uPAR is required for maintenance of its sub nanomolar affinity for uPA , but the functional epitope for this interaction is primarily located in uPAR domain 1 . ^^^ Using affinity maturation by combinatorial chemistry , we have recently identified a potent 9 mer peptide antagonist of the uPA uPAR interaction having a high affinity for uPAR ( K ( d ) < 1 nM ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Adhesion molecules ( E cadherin , catenins , serum intercellular adhesion molecule 1 , CD 44 variants ) , proteinases involved in the degradation of extracellular matrix ( MMP 2 , MMP 9 , uPA , uPAR , PAI ) , as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC , and are related to prognosis and therapeutic outcomes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In cranial sutural samples derived from five children with premature cranial suture fusion we have performed immunostaining for the urokinase plasminogen activator ( uPA ) and urokinase receptor ( uPAR ) . ^^^ We have found a strong reactivity for cell or matrix bound uPA and uPAR in the sutural connective tissue and associated with the osteoblasts and osteocytes lining the calvarial bone . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Northern blot analysis demonstrated that genes encoding urokinase type plasminogen activator ( uPA ) , urokinase type plasminogen activator receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , tissue inhibitor of metalloproteinases ( TIMP 1 ) and c myc were up regulated in response to hyaluronan . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of UPA and UPAR is associated with the clinical course of urinary bladder neoplasms . ^^^ The expression of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) mRNA was determined in 194 subjects with newly detected bladder neoplasms , selected from a larger population based series . ^^^ An association was found between uPA and uPAR expression ( n = 172 ; Spearman r ( s ) = 0 . 60 , p < 0 . 001 ) . ^^^ Both uPA and uPAR mRNA levels were higher in muscle invasive ( T2+ ) tumors than in noninvasive mucosal tumors ( Ta ) or those invading submucosa ( T 1 ) . ^^^ The relative hazard ratios ( RHRs ) for cancer specific death associated with elevated expression ( 95 % CI ) , adjusted for age and gender in a Cox proportional hazard model , were 1 . 8 ( 1 . 0 3 . 3 ) for uPA ( upper quartile cut line ) , 2 . 2 ( 1 . 3 4 . 0 ) for uPAR ( median quartile cut line ) and 2 . 5 ( 1 . 3 4 . 9 ) for uPA + uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) , its inhibitors ( PAI 1 and PAI 2 ) , and its receptor ( uPAR ) play a key role in tumor invasion and metastasis . ^^^ This study was designed to evaluate the prognostic impact of uPA , PAI 1 , PAI 2 , and uPAR and the combination of these factors in a group of 460 primary breast cancer patients . ^^^ The other 2 invasion markers , uPA and uPAR , showed no statistically significant impact on DFS . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Invasive tumor cells produce a large amount of uPA that could bind uPAR present at the endothelial cell surface to facilitate their invasion . ^^^ The uPA increase in the cell layer could not be attributable to an increase of uPAR level . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In contrast , the blood pressure of urokinase receptor knockout ( uPAR ( / ) ) mice and the response of their isolated aortic rings to phenylephrine were normal , indicating that the effect of uPA on vascular contraction is independent of uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition , we identified MMP 9 , uPA , uPAR , cyclin D 1 and S100A4 ( mts 1 ) as possible contributors of the metastatic phenotype . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We elected to see if the extra cellular domain of HER 2 / neu , the p 105 fraction , which is found in the circulation , has any regulatory influence on uPA or uPAR in those patients with NSCLC Levels of uPA , uPAR and p 105 HER 2 / neu were determined in blood from age matched controls and patients with advanced NSCLC . ^^^ A large increase in both uPA and uPAR compared to controls was seen in the patients prior to treatment . ^^^ Additionally , correlation analysis of circulating uPAR , uPA and HER 2 / neu against each other in both the controls and treatment groups indicated no relationship . ^^^ It appears that circulating uPA and uPAR are elevated in NSCLC patients . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To test this hypothesis , we examined whether bikunin was able to suppress the expression of uPA receptor ( uPAR ) mRNA and protein in a human chondrosarcoma cell line , HCS 2 / 8 , and two human ovarian cancer cell lines , HOC 1 and HRA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of urokinase ( uPA ) and its receptor ( uPAR ) is associated with increased tumor cellinvasion and metastasis in several malignancies including breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The role of uPA and its receptor ( CD 87 ) in plasminogen ( Plg ) activation , cell adhesion , and chemotaxis is well established ; however , less is known of how these activities are regulated . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We found that mLRP1B4 and urokinase plasminogen activator receptor ( uPAR ) form immunoprecipitable complexes on the cell surface in the presence of complexes of uPA and its inhibitor , plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Expression of mLRP1B4 , or an mLRP 4 mutant deficient in endocytosis , leads to an accumulation of uPAR at the cell surface and increased cell associated uPA and PAI 1 when compared with cells expressing mLRP 4 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Proteolytic cleavage of the urokinase plasminogen activator receptor ( uPA ( R ) ) prevents the binding of uPA and vitronectin while generating biologically active uPAR fragments . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition to aspartyl and cysteineproteinases , serine proteinases including the plasminogen activator system ( uPA , uPAR , tPA , PAI 1 and PAI 2 ) and matrix metalloproteinases ( MMPs ) with their tissue inhibitors ( TIMPs ) play an essential role in these processes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Its major components are urokinase ( uPA ) and tissue type plasminogen activator ( tPA ) , plasminogen activation inhibitor type 1 and 2 ( PAI 1 and PAI 2 ) and a receptor for urokinase ( uPAR ) . ^^^ Spitz naevi had melanocytic positivity for uPA in 0 % ( 0 / 36 ) , tPA in 30 % ( 6 / 20 ) , PAI 1 in 10 % ( 3 / 35 ) , PAI 2 in 40 % ( 8 / 21 ) and uPAR in 60 % ( 13 / 21 ) of cases . ^^^ This was much ( for most components significantly ) less than the proportion of primary melanomas with tumour cell positivity , which was 30 % ( 11 / 38 ) for uPA , 80 % ( 19 / 24 ) for tPA , 75 % ( 28 / 38 ) for PAI 1 , 80 % ( 19 / 24 ) for PAI 2 and 80 % ( 19 / 24 ) for uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase plasminogen activator ( uPAR ) serves to localise and intensify the action of uPA and is expressed on the surface of malignant as well as tumour stromal cells including fibroblasts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) binds with high affinity to its specific cell surface receptor ( uPAR ) ( CD 87 ) via a well defined sequence within the N terminal region of uPA ( uPA ( 19 31 ) ) . ^^^ Since this uPA / uPAR interaction plays a significant role in tumor cell invasion and metastasis , it has become an attractive therapeutic target . ^^^ Two small peptidic cyclic competitive antagonists of uPA / uPAR interaction have been developed , based on the uPAR binding site in uPA : WX 360 ( cyclo ( 21 , 29 ) [ D Cys 21 ] uPA ( 21 30 ) [ S21C ; H29C ] ) and its norleucine ( Nle ) derivative WX 360 Nle ( cyclo ( 21 , 29 ) [ D Cys 21 ] uPA ( 21 30 ) [ S21C ; K23Nle ; H29C ] ) . ^^^ These peptides display an only five to 10 fold lower affinity to uPAR as compared to the naturally occurring uPAR ligand uPA . ^^^ This is the first report demonstrating effective reduction of tumor growth and spread of human ovarian cancer cells in vivo by small synthetic uPA derived cyclic peptides competitively interfering with uPA / uPAR interaction . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) is able to cleave its cell surface receptor ( uPAR ) anchored to the cell membrane through a glycophosphatidylinositol tail . ^^^ The expression of intact and truncated uPARs regulated cell directional migration toward uPA , the specific uPAR ligand , and toward fMLP , a bacterial chemotactic peptide . ^^^ In fact , the uPA dependent cell migration required the expression of intact uPAR , including D 1 , whereas the fMLP dependent cell migration required the expression of a P 88 92 containing uPAR and was independent of the presence of D 1 . ^^^ Together these observations indicate that uPA mediated uPAR cleavage and D 1 removal , occurring on the cell surface of several cell types , can play a fundamental role in the regulation of multiple uPAR functions . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
EGF also induced increased expression of uPA and uPA receptor ( uPAR ) proteins and mRNA , as well as transcription factor activator protein 1 ( AP 1 ) DNA binding . ^^^ Moreover , transfection of SCC cells with AP 1 decoy oligodeoxynucleotides ( ODNs ) resulted in the suppression of EGF induced uPA and uPAR expression and Matrigel invasion . ^^^ The uPA uPAR interaction is essential for augmenting proteolytic activity and uPAR mediated signaling , which ultimately induce motility and invasion . ^^^ Since DEX inhibits the expression of both uPA and uPAR , it may be a useful treatment for oral SCC . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we used human peripheral blood neutrophils and transfected cells expressing alpha ( M ) beta ( 2 ) , uPAR , or both receptors to show that the integrin can directly interact with urokinase ( uPA ) . ^^^ Within uPA , both the kringle and proteolytic domains are recognized by alpha ( M ) beta ( 2 ) , which are distinct from the growth factor domain that binds to uPAR . ^^^ Within the alpha ( M ) subunit of the integrin , the 1 domain interacts with uPA , which is distinct from the region that interacts with uPAR . ^^^ This cooperation was particularly apparent in the responses of neutrophils to uPA , where blockade of alpha ( M ) beta ( 2 ) reduced uPAR mediated responses and engagement of uPAR enhanced recognition of uPA by alpha ( M ) beta ( 2 ) . ^^^ Thus , recognition of uPA by alpha ( M ) beta ( 2 ) allows for formation of a multicontact trimolecular complex , in which a single uPA ligand may bind simultaneously to both uPAR and alpha ( M ) beta ( 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In our study , we have studied the effects of CD 44 stimulation by ligation with HA upon the expression of matrix metalloproteinases ( MMPs ) 2 and 9 as well as urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) and its inhibitor ( PAI 1 ) and the subsequent induction of invasion of human chondrosarcoma cell line HCS 2 / 8 . ^^^ Therefore , our study represents the first report that CD 44 stimulation induced by a fragmented HA results in activation of MAP kinase and , subsequently , enhances uPA and uPAR expression and facilitates invasion of human chondrosarcoma cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Tumor tissues from 71 patients with CRC were assayed to determine the antigen levels of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 and 2 ( PAI 1 and PAI 2 ) , as well as immunohistochemical expression of VEGF . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Tumor cell migration and metastasis in cancer are facilitated by interaction of the serine protease urokinase type plasminogen activator ( uPA ) with its receptor uPAR ( CD 87 ) . ^^^ Overexpression of uPA and uPAR in cancer tissues is associated with a high incidence of disease recurrence and early death . ^^^ In agreement with these findings , disruption of the protein protein interaction between uPAR present on tumor cells and its ligand uPA evolved as an attractive intervention strategy to impair tumor growth and metastasis . ^^^ For this , the uPAR antagonist cyclo [ 19 , 31 ] [ D Cys ( 19 ) ] uPA ( 19 ) ( ) ( 31 ) was optimized to efficiently interrupt binding of uPA to cellular uPAR . ^^^ For analysis of uPAR binding activity , we employed competitive flow cytofluorometric receptor binding assays , using FITC uPA as the ligand and U 937 promyeloid leukemia cells as the cellular source of uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , Ganoderma inhibition of expression of uPA and uPA receptor ( uPAR ) , as well secretion of uPA , resulted in the suppression of the migration of MDA MB 231 and PC 3 cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase type plasminogen activator ( uPA ) to its receptor ( uPAR ) on the surface of tumor cells is involved in the activation of proteolytic cascades responsible for the invasiveness of those cells . ^^^ The diffuse , extensive infiltration of glioblastomas into the surrounding normal brain tissue is believed to rely on modifications of the proteolysis of extracellular matrix components ; blocking the interaction between uPA and uPAR might be a suitable approach for inhibiting glioma tumorigenesis . ^^^ We assessed how expression of an amino terminal fragment ( ATF ) of uPA that contains binding site to uPAR affects the invasiveness of SNB 19 human glioblastoma cells . ^^^ ATF uPA transfectants were also markedly less invasive than parental SNB 19 cells after injection into the brains of nude mice , suggesting that competitive inhibition of the uPA uPAR interaction on SNB 19 cells by means of transfection with ATF cDNA could be a useful therapeutic strategy for inhibiting tumor progression . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and vitronectin activate cell signaling pathways by binding to the uPA receptor ( uPAR ) . ^^^ The goal of this study was to elucidate the role of the EGF receptor ( EGFR ) as a component of the uPAR signaling machinery . uPA activated extracellular signal regulated kinase ( ERK ) in COS 7 cells and in COS 7 cells that overexpress uPAR , and this response was blocked by the EGFR inhibitor , tyrphostin AG 1478 , implicating the EGFR in the pathway that links uPAR to ERK . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : CSF and serum concentrations of urokinase plasminogen activator ( urokinase [ uPA ] ) , uPA receptor ( uPAR ) , and PA inhibitor 1 ( PAI 1 ) were quantified by ELISA in 12 patients with bacterial meningitis , control patients ( n = 10 ) with noninflammatory neurologic diseases , and 10 patients with Guillain Barr syndrome ( GBS ) , a disease in which blood CSF barrier disruption occurs without CSF pleocytosis . ^^^ The serum of patients with bacterial meningitis showed elevated protein levels of uPA , but not uPAR or PAI 1 . ^^^ Positive correlations were found between blood CSF barrier breakdown and CSF uPA concentrations , and between CSF pleocytosis and CSF / serum ratios of the potent chemokine uPAR in patients with bacterial meningitis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Correspondingly , the autocrine cells were highly tumorigenic in vivo compared to the parental and non autocrine cells , which correlated with the increased production of uPAR and active uPA and increased in vitro invasive potential . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The number of uPA receptors ( uPAR or CD 87 ) was measured using a phycoerythrin conjugated monoclonal antibody to CD 87 and flow cytometry . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To study the expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in the synovial tissures , and the significance of uPA and uPAR in degradation of extracellular matrices in osteoarthritis ( OA ) , then analyse the possible relationship between uPA and uPAR . ^^^ METHODS : Immunohistochemical analysis technique was used to detect uPA and uPAR protein expression and distribution in synovial tissues in 26 OA patients and 10 mormal individuals . ^^^ RESULTS : Positive staining of uPA and uPAR protein were detected in 19 cases in the 26 OA samples ( 73 % ) , while only 2 positive cases were seen in the 10 mormal tissues ( 20 % ) . ^^^ Positive expression of uPA and uPAR proteins were found in synovial lining cells , mononuclear cells , macrophage like cells and endothelial cells . ^^^ Using the correction analysis , we found a positive correlation between uPA and uPAR reactivity in the synovial tissues in OA ( r = 0 . 920 , P < 0 . 01 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding between uPA and its receptor uPAR also mediates several signaling events that seem to contribute to the evolution of a migratory phenotype . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Rb 2 may stimulate the secretion of uPA without enhancing the gene expression of uPA , uPA receptor ( uPAR ) , and PAI 1 . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Our previous study revealed that overexpression of bikunin in a human ovarian cancer cell line , HRA , resulted in a down regulation in uPA and uPAR gene expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Stromal cells also contribute to breast cancer growth and metastasis through the production of extracellular matrix ( ECM ) modifiers such as urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , its inhibitors ( PAI 1 and PAI 2 ) , matrix metalloproteinases ( MMPs ) , and growth factors , including the fibroblast and insulin like growth factors ( FGF ' s and IGF ' s ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The delayed , but not the early phase of VEGF induced permeability , was blocked by anti uPA or anti uPAR ( uPA receptor ) antibodies and was accompanied by reduced transendothelial electrical resistance , indicating the paracellular route of permeability . ^^^ Membrane bound occludin was released immediately after uPA treatment , but with a long delay after VEGF treatment , suggesting a requirement for uPAR gene expression . ^^^ In conclusion , VEGF induces a sustained paracellular permeability in capillary endothelial cells that is mediated by activation of the uPA / uPAR system . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Moreover , using cells deficient for uPA receptor ( uPAR ) we have demonstrated that the inhibition of PAI 1 on insulin signaling is independent of uPAR VN binding . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase plaminogen activator ( uPA ) to its cell surface receptor ( uPAR ; CD 87 ) promotes cell adhesion by increasing the affinity of the receptor for both vitronectin ( VN ) and integrins . ^^^ We provide evidence that plasminogen activator inhibitor ( PAI ) 1 can detach cells by disrupting uPAR VN and integrin VN interactions and that it does so by binding to the uPA present in uPA uPAR integrin complexes on the cell surface . ^^^ Immunoprecipitation and subcellular fractionation experiments reveal that PAI 1 treatment triggers deactivation and disengagement of uPA uPAR integrin complexes and their endocytic clearance by the low density lipoprotein receptor related protein . ^^^ Transfection experiments demonstrate that efficient cell detachment by PAI 1 requires an excess of matrix engaged uPA uPAR integrin complexes over free engaged integrins and that changes in this ratio alter the efficacy of PAI 1 . ^^^ Together , these results suggest a VN independent , uPA uPAR dependent mechanism by which PAI 1 induces cell detachment . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : Protein expression of the PAS , including urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , plasminogen ( Plg ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 and PAI 2 ) , was determined in the colonic tissue samples of 56 patients with resected primary CRC by quantitative immunohistochemistry and correlated with clinicopathological parameters and patient outcome . ^^^ RESULTS : Overexpression of uPA ( t test , P < 0 . 001 ) , uPAR ( P < 0 . 001 ) and PAI 1 ( P = 0 . 031 ) was significantly associated with liver metastatic CRC tumors . ^^^ Higher uPA or uPAR expression level was significantly correlated with overall survival ( OS ; log rank , P = 0 . 001 and P < 0 . 0001 ) and cancer specific survival ( CSS ; P = 0 . 001 and P < 0 . 0001 ) after the first CRC resection . ^^^ The predictive value of both uPA and uPAR in liver metastasis , OS and CSS was independent from other parameters ( multivariate Cox regression : all P < 0 . 001 ) . ^^^ CONCLUSIONS : uPA and uPAR may be independent predictors of liver metastasis , patient overall survival and cancer specific survival after resection of colorectal tumors . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) strongly correlates with a malignant tumour cell phenotype . ^^^ In the multistep process of metastasis , uPA binding to uPAR influences different cellular functions . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasminogen / plasmin system , urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , and its inhibitor ( PAI 1 ) , influence extracellular proteolysis and cell migration in lung injury or neoplasia . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) system , which consists of a proteinase ( uPA ) , a receptor ( uPAR or CD 87 ) and inhibitors , is involved in proteolysis , cell migration , tissue remodelling , angiogenesis and cell adhesion . ^^^ Recent findings suggest that malignant plasma cells express uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The influence of endogenous plasminogen ( Plg ) , urokinase ( uPA ) , tissue type plasminogen activator ( tPA ) , and uPA receptor ( uPAR ) was explored in single gene deficient mice in a model of laser induced CNV . ^^^ The absence of Plg , uPA , or tPA significantly decreased the development of experimental CNV compared with wild type or uPAR deficient mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The proliferative balance of high ERK / p38 ratio was induced by high urokinase ( uPA ) receptor ( uPAR ) expression , which activated alpha5beta1 integrin and epidermal growth factor receptor . ^^^ This signaling pathway was additionally enhanced by uPA binding to uPAR and fibronectin binding to alpha5beta1 integrin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) are instrumental in cellular activities during inflammation , angiogenesis and tumor metastasis . ^^^ Recent studies suggest that uPA might exert its function on cell proliferation and migration in a uPAR independent manner or through an adaptor to the uPA uPAR system . ^^^ By applying phage display technology , we have identified a putative uPA binding consensus sequence BXXSSXXB ( where B represents a basic amino acid and 10 represents any amino acid ) , which has no apparent sequence correlation to uPAR . ^^^ This uPA binding motif apparently recognizes the kringle domain of the protease and has an agonistic effect on uPA binding to immobilized uPAR , thereby possibly serving as part of an adaptor component for uPAR signaling . ^^^ As a result of protein database searches , this motif was found in the extracellular domain of several cell surface proteins , some of which were proposed to be associated with the uPA uPAR system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
All inhibitors that were tested ( active site inhibitors directed against uPA , tPA , and / or plasmin ; antibodies neutralizing the enzymatic activity of uPA or tPA ; substances interfering with the binding of uPA to its specific cell surface receptor uPAR ) failed to prevent pemphigus vulgaris IgG mediated acantholysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Newly described pathways by which lung epithelial cells regulate expression of uPA , its receptor uPAR , and PAI 1 at the posttranscriptional level have been identified . ^^^ The regulatory mechanisms seem to involve multiple protein mRNA interactions , and the phosphorylation state of the proteins appears to determine whether complex formation of , or dissociation from , the regulatory sequences occurs . uPA is capable of inducing its own expression in lung epithelial cells as well as that of uPAR and PAI 1 the effects involve posttranscriptional regulatory components . ^^^ Expression of uPA , uPAR , and PAI 1 by the lung epithelium , as well as the ability of uPA to induce other components of the fibrinolytic system , involves posttranscriptional regulation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To define the role of the plasminogen activators ( PAs ) urokinase PA ( uPA ) and tissue PA ( tPA ) as well as the uPA receptor ( uPAR ) in arteriogenesis , we investigated their impact in a rabbit and mouse model of adaptive collateral artery growth . ^^^ Collateral artery growth was induced by occlusion of the femoral artery in rabbit and wild type ( WT ) mice and in mice with targeted inactivation of uPA ( uPA / ) , tPA ( tPA / ) , or uPAR ( uPAR / ) . ^^^ Northern blot results revealed a significant up regulation of uPA but not uPAR or tPA in the early phase of arteriogenesis in rabbit and WT mice . ^^^ Impaired perfusion recovery upon femoral artery ligation was observed by laser Doppler analysis in vivo in uPA deficient mice but not in uPAR or tPA deficiency compared with WT mice . ^^^ Immunohistochemical studies revealed an association of leukocyte infiltration with arteriogenesis in WT mice that was strongly reduced in uPA / but not in uPAR or tPA deficient mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor uPAR are components of the fibrinolytic system and are important for an adequate immune response to respiratory tract infection , in part through their role in the migration of inflammatory cells . ^^^ These data indicate that pneumonia is associated with inhibition of the fibrinolytic system at the site of the infection secondary to increased production of PAI 1 ; an intact fibrinolytic response is not required for an adequate host response to respiratory tract infection , however , suggesting that the previously described role of uPA and uPAR are restricted to their function in cell migration . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The ratios of immunopositive cells of uPA and uPA receptor ( uPAR ) were not significantly different among the groups . uPA and uPAR were found to be positive in a different set of SMCs of the MMP 9 positive cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and its cellular receptor ( uPAR ) are involved in the proteolytic cascade required for tumor cell dissemination and metastasis , and are highly expressed in many human tumors . ^^^ We have recently reported that uPA , independently of its enzymatic activity , is able to increase the expression of its own receptor in uPAR transfected kidney cells at a posttranscriptional level . ^^^ In fact , uPA , upon binding uPAR , modulates the activity and / or the level of a mRNA stabilizing factor that binds the coding region of uPAR mRNA . ^^^ We now investigate the relevance of uPA mediated posttranscriptional regulation of uPAR expression in non small cell lung carcinoma ( NSCLC ) , in which the up regulation of uPAR expression is a prognostic marker . ^^^ We show that uPA is able to increase uPAR expression , both at protein and mRNA levels , in primary cell cultures obtained from tumor and adjacent normal lung tissues of patients affected by NSCLC , thus suggesting that the enzyme can exert its effect in lung cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of this study was to determine the expression of proteinases and inhibitors from the matrix metalloproteinase ( MMP ) ( MMPs 1 , 2 , 3 , 9 , tissue inhibitors of metalloproteinases ( TIMPs ) 1 , 2 ) and plasminogen activator ( ( PA ) urokinase ( uPA ) , tissue type ( tPA ) , uPAR , plasminogen activator inhibitors ( PAIs ) 1 , 2 ) systems in colorectal cancer pathology by gelatin zymography , enzyme linked immunosorbent assays ( ELISAs ) and quenched fluorescent substrate hydrolysis . ^^^ The levels of all studied MMPs , uPA , uPAR , TIMP 1 and PAIs were significantly greater in tumour tissues than normal tissues . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These data suggest that uPAR deficiency suppresses renal Mphi recruitment , but the absence of this scavenger receptor actually accentuates the fibrogenic response , likely due in part to the delayed clearance of angiogenic / profibrotic molecules such as PAI 1 and decreased receptor associated uPA activity . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase cellular receptor ( uPAR ) recognizes the N terminal growth factor domain of urokinase type plasminogen activator ( uPA ) and is expressed by several cell types . ^^^ In the absence of uPAR , renal uPA activity was significantly decreased compared with the wild type animals after UUO ( 62 + / 20 versus 135 + / 13 units at day 3 UUO ; 74 + / 17 versus 141 + / 16 at day 7 UUO ; 98 + / 20 versus 165 + / 10 at day 14 UUO ; / versus + / + ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Cancer tissues from 101 gastric cancer patients were assayed immunohistochemically for expression of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , PA inhibitor 1 ( PAI 1 ) and VEGF protein . ^^^ The positive rates of uPA , uPAR , PAI 1 , VEGF expression were 22 . 8 % , 32 . 7 % , 36 . 6 % and 26 . 7 % , respectively . ^^^ Positive staining was observed in tumor cells ( uPA , uPAR , VEGF ) , or in both tumor cells and stromal cells ( PAI 1 ) . ^^^ The expressions of uPA , uPAR , PAI 1 and VEGF were significantly correlated with the clinicopathological factors : uPA , depth of tumor invasion , differentiation , lymphatic and vascular invasion ; uPAR , tumor size , depth , lymph node involvement , differentiation , vascular invasion ; PAI 1 , tumor size , depth , lymph node involvement , differentiation , vascular invasion ; VEGF , differentiation , vascular invasion . ^^^ The microvessel density ( MVD ) assessed immunohistochemically was significantly higher in the patients with expression of uPA , uPAR or VEGF , and stepwise analysis identified uPA as an independent correlated factor with MVD . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In human vascular smooth muscle cell ( VSMC ) uPA stimulates migration via the uPA receptor ( uPAR ) signalling complex containing the Janus kinase Tyk 2 and phosphatidylinositol 3 kinase ( PI 3 K ) . ^^^ We report that active GTP bound forms of small GTPases RhoA and Rac 1 , but not Cdc 42 , are directly associated with Tyk 2 and PI 3 K in an uPA / uPAR dependent fashion . ^^^ Our results provide evidence that the small GTPases RhoA and Rac 1 , together with Rho kinase , are necessary to mediate the uPA / uPAR directed migration via the Tyk2 / PI3 K signalling complex in human VSMC . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A highly polarized expression of uPAR bound uPA at the migration front of EVT cells in situ suggests a functional role of uPA : uPAR interaction in EVT cell migration . ^^^ Migration was found to be stimulated by hypoxic conditions , which upregulates uPAR expression ; this stimulation was abrogated with the uPAR blocking antibody , indicating the role of endogenous uPA in EVT cell migration . ^^^ Taken together , these results demonstrate that uPA : uPAR interaction stimulates EVT cell migration , independent of uPA enzymatic activity , using the mitogen activated protein kinase pathway and calcium signaling events including the participation of PI 3 K and PLC . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We tested the hypothesis that preoperative plasma levels of uPA and its specific receptor , uPAR , would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder . ^^^ Preoperative plasma levels of uPA and uPAR were measured by enzyme linked immunosorbent assay in patients with available samples ( 51 and 38 , respectively ) and correlated with the clinical and pathologic characteristics and clinical outcome . ^^^ RESULTS : Plasma uPA and uPAR levels were both greater in those with bladder cancer than in the healthy subjects ( P < 0 . 001 ) . ^^^ Preoperative uPA was independently associated with metastases to regional lymph nodes ( P = 0 . 017 ) , lymphovascular invasion ( P = 0 . 019 ) , disease progression ( P = 0 . 030 ) , and death from bladder cancer ( P = 0 . 038 ) . uPAR was not associated with bladder cancer outcome . ^^^ CONCLUSIONS : Plasma uPA and uPAR levels were greater in those with bladder cancer compared with healthy controls . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase plasminogen activator ( uPA ) to its receptor ( uPAR ) initiates a proteolytic cascade facilitating the activation of matrix metalloproteinase 9 ( MMP 9 ) , which in turn degrades the extracellular matrix . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Critical role of integrin alpha 5 beta 1 in urokinase ( uPA ) / urokinase receptor ( uPAR , CD 87 ) signaling . ^^^ Urokinase type plasminogen activator ( uPA ) induces cell adhesion and chemotactic movement . uPA signaling requires its binding to uPA receptor ( uPAR / CD87 ) , but how glycosylphosphatidylinositol anchored uPAR mediates signaling is unclear . uPAR is a ligand for several integrins ( e . g . alpha 5 beta 1 ) and supports cell cell interaction by binding to integrins on apposing cells ( in trans ) . ^^^ We studied whether binding of uPAR to alpha 5 beta 1 in cis is involved in adhesion and migration of Chinese hamster ovary cells in response to immobilized uPA . ^^^ Anti uPAR antibody or depletion of uPAR blocked , whereas overexpression of uPAR enhanced , cell adhesion to uPA . ^^^ Interestingly , anti alpha 5 antibody , RGD peptide , and function blocking mutations in alpha 5 beta 1 blocked adhesion to uPA . uPA induced cell migration also required GFD , uPAR , and alpha 5 beta 1 , but alpha 5 beta 1 alone did not support uPA induced adhesion and migration . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Amyloid beta protein stimulates the expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in human cerebrovascular smooth muscle cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and the uPA receptor ( uPAR ) are involved in a proteolytic cascade resulting of extracellular matrix degradation . ^^^ Upstream , uPA and uPAR are regulated by various factors including hepatocyte growth factor ( HGF ) , which stimulates the uPA / uPAR proteolytic system and increases invasion of cancers . ^^^ We therefore examined effects of HGF on uPA and uPAR expression in DU 145 cells . ^^^ Effects of HGF on uPA expression in culture medium were determined by Western blotting and fibrin zymography , effects on uPAR expression in cell associated protein were examined by Western blotting . ^^^ HGF increased uPA and uPAR production in a dose dependent manner up to 10 ng / mL , while effects of 20 ng / mL were approximately equal to those of 10 ng / mL . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase type plasminogen activator ( uPAR ) plays important roles in a number of physiological and pathological processes by virtue of its interactions with urokinase type plasminogen activator ( uPA ) , vitronectin ( Vn ) , and several other proteins . ^^^ The uPA binding site spans all three domains ( D 1 to D 3 ) of uPAR . ^^^ Most importantly , we found two unique mutants uPAR ( Asn 172 Lys175 ) and uPAR ( Glu 183 Asn186 ) within the D 2 domain , which displayed differential ligand binding activity : both had high affinity uPA binding , but completely lost Vn binding , indicating that these two sequences constitute a novel Vn binding site . ^^^ Indeed , two peptides , P 1 ( 153CPGSNGFHNNDTFHFLKC ) and P 2 ( 171CNTTKCNEGPILELENLPQ ) , derived from the sequences of the identified uPA and Vn binding pockets within D 2 , respectively , behaved like bona fide ligand binding sites : peptide P 1 bound uPA but not Vn , whereas peptide P 2 bound Vn and inhibited uPAR mediated cell adhesion , but did not interact with uPA . ^^^ Altogether , our data demonstrated that uPAR D 2 contains two distinct ligand binding sites for uPA and Vn . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The mechanism of pro MMP 2 activation in glioma astrocyte coculture was investigated and was found to involve the urokinase type plasminogen activator ( uPA ) plasmin cascade whereby uPA bound to uPA receptor ( uPAR ) , leading to the conversion of plasminogen to plasmin . ^^^ Furthermore , key components ( i . e . , uPAR , uPA , and pro MMP 2 ) were contributed principally by astrocytes , whereas the U251N glioma cells provided plasminogen . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PURPOSE : The objective of the study was to determine the role of urokinase ( uPA ) and the urokinase receptor ( uPAR ) in retinal angiogenesis , and whether loss of uPAR or the inhibition of uPA / uPAR interactions could suppress the extent of retinal neovascularization in an animal model of ischemic retinopathy . ^^^ The effects of inhibiting the uPA / uPAR interaction on the development of retinal neovascularization were studied in this animal model with a uPA derived peptide , A 6 . ^^^ The uPA / uPAR interaction may be an important therapeutic target in the management of proliferative retinopathies . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The subject of this review , the urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , plays an impressive range of distinct , but overlapping functions in the process of cancer invasion and metastasis : Firstly , uPA / uPAR promotes extracellular proteolysis by regulating plasminogen activation . ^^^ Secondly , uPA / uPAR regulates cell / ECM interactions as an adhesion receptor for vitronectin ( Vn ) and through its capacity to modulate integrin function . ^^^ Thirdly , uPA / uPAR regulates cell migration as a signal transduction molecule and by its intrinsic chemotactic activity . ^^^ This review is focused on recent insight into the cancer related biology of the uPA / uPAR system as well as its implications for clinical cancer diagnosis , prognosis and therapy . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The tumor cell associated urokinase type plasminogen activator system , consisting of the serine protease uPA , its substrate plasminogen , its membrane bound receptor uPAR , as well as its inhibitors PAI 1 and PAI 2 , plays an important role in these pericellular processes . ^^^ Especially , association of the proteolytic activity of uPA with the cell surface via interaction with uPAR significantly increases the invasive capacity of tumor cells . ^^^ Consequently , various approaches have been pursued to interfere with the expression or activity of uPA and / or uPAR , including antisense strategies and the development of active site inhibitors of uPA or inhibitors of uPA / uPAR interaction . ^^^ In this review , we focus on the results obtained in vitro and in vivo with tumor cells producing high levels of a recombinant soluble form of uPAR , which efficiently inhibits uPA binding to cell surface associated uPAR and , by this , acts as a scavenger for uPA . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It consists of the serine protease uPA , its membrane bound receptor ( uPAR , CD 87 ) and one of the natural inhibitors PAI 1 or PAI 2 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Interaction between urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) localizes cellular proteolysis and promotes cellular proliferation and migration , effects that may contribute to the pathogenesis of lung inflammation and neoplasia . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
CD 87 is a widely expressed receptor for urokinase plasminogen activator ( uPA ) and plays a critical role in regulation of cell surface plasminogen activation . ^^^ The association of CD 87 overexpression in tumor cells with tumor invasion has attracted many researchers to exploration of the potential therapeutic utility of CD 87 by targeting binding of CD 87 to uPA , the interactions between CD 87 and other surface and matrix molecules , CD 87 gene expression , and posttranscriptional modification . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
EGF stimulation also resulted in increased uPAR transcript in both cell lines . uPA production and activity were suppressed by the inhibitor to well below the levels in control cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Human T blasts and SupT 1 lymphoma cells expressed mRNA of MMP 9 , MT 1 MMP , MT 4 MMP , cathepsin L , uPA , and uPAR as well as ADAM 9 , 10 , 11 , 15 , and 17 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We assessed the expression of uPAR / beta1 integrin complex , Erk signalling pathway , adhesion , uPA and matrix metalloproteinase ( MMP ) expression , migration / invasion and matrix degradation in a colon cancer cell line in which uPAR expression was modified . ^^^ Disruption of uPAR beta 1 integrin complex in mock transfected cells with a specific peptide ( P 25 ) inhibited uPA mediated Erk MAP kinase pathway and inhibited migration / invasion and plasmin dependent matrix degradation through suppression of pro MMP 9 / MMP 2 expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of a high affinity , glycolipid anchored receptor for the urokinase type plasminogen activator ( uPAR ) is often up regulated during such tissue remodeling events . uPAR may , therefore , in cooperation with various matrix metalloproteases , serve to facilitate the proteolytic breakdown of the extracellular matrix via uPA catalyzed plasminogen activation at the foci where cellular invasion occurs . ^^^ Consistent with such a role for uPAR in pericellular proteolysis is the observation that the membrane assembly of both plasminogen , via its lysine binding sites , and of pro uPA , via its tight binding to uPAR , is required to favor and confine plasminogen activation potential in proximity of the cell surface . ^^^ Furthermore a mapping of the functional epitopes for uPA binding as well as a competitive peptide antagonist of the uPA uPAR interaction will be discussed . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The purified fusion protein inhibited urokinase type plasminogen activator as measured by milk agarose plate assay , and bound to human lung cancer cells via uPA receptor ( uPAR ) , which was confirmed by radio competition experiments . ^^^ The results indicate that the biological characteristics of ATF PAI2CD were very similar to those of the wide type PAI 2 ( or mutants PAI 2 , PAI 2CD ) and to pro uPA in binding to uPAR bearing cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , paraffin embedded material from 84 human pituitary adenomas ( acromegaly n=18 , Cushing ' s disease n=21 , prolactinoma n=18 , thyroid stimulating hormone secreting adenoma n=1 , nonsecreting adenoma n=26 ) and 9 nontumourous anterior pituitary lobes ( obtained from patients with prostate cancer ) was immunohistochemically analysed for expression of MMP 2 , MMP 9 , tissue inhibitor of metalloproteinases 2 ( TIMP 2 ) , urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and interleukin 6 ( IL 6 ) . ^^^ In pituitary adenomas , reactions were positive ( diffuse expression ) to MMP 2 ( 74 % of cases ) , MMP 9 ( 49 % ) , TIMP 2 ( 88 % ) , uPA ( 89 % ) , uPAR ( 90 % ) , tPA ( 69 % ) , and PAI 1 ( 87 % ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The overexpression of MIC 1 into SNU 216 cells significantly increased the activity of urokinase type plasminogen activator ( uPA ) , and the expressions of uPA and urokinase type plasminogen activator receptor ( uPAR ) . ^^^ Similarly , the stimulation of gastric cancer cell lines with purified recombinant MIC 1 dose dependently increased cell invasiveness , uPA activity , and uPA and uPAR expression . ^^^ Additional analysis revealed that PD 98059 , a selective inhibitor of mitogen activated protein kinase kinase 1 / 2 , suppressed not only gastric cancer cell invasiveness and uPA activity , but also the mRNA expressions of uPA and uPAR , as induced by recombinant MIC 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , the cells did not express receptors including types 1 and 2 TNF alpha receptors , uPA receptor ( uPAR ) , C 10 C chemokine receptor 1 ( CXCR 1 ) , or C C chemokine receptor 2 , corresponding to TNF alpha , uPA , IL 8 and MCP 1 , respectively , that were induced by doxorubicin in the cells , although SBC 7 cells expressed uPAR , and EBC 1 cells expressed CXCR 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : Angiogenesis was assessed in gene targeted mice with deficiencies of plasminogen , urokinase plasminogen activator ( uPA ) , and urokinase receptor ( uPAR ) in a mouse corneal model . ^^^ RESULTS : In response to angiogenic stimulation by basic fibroblast growth factor ( bFGF ) , uPA deficient mice exhibited a decrease in new vessel formation as reflected by vessel length ( 0 . 47 in control vs . 0 . 33 mm in uPA / mice , P = 0 . 043 ) , but new vessel formation was not altered ( P = 0 . 107 ) in the uPAR deficient mice compared to control mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We used a rat Achilles tendon model to study mRNA and protein expression of uPA and its receptor ( uPAR ) during tendon healing using immunohistochemical , Northern and Western blot analyses . ^^^ Time dependent increases in uPA / uPAR mRNAs and proteins , maximal on days 4 7 and 7 14 respectively , were found following Achilles tendon division . ^^^ Interestingly , uninjured control tendons expressed uPA mRNA and protein , but little uPAR transcripts and protein . ^^^ Immunohistochemical analyses revealed that both uPAR / uPA positive staining cells were increased in the healing tendon tissue section . ^^^ These findings show for the first time that uPA , and especially its receptor uPAR , are up regulated during tendon healing . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The VSMC uPA receptor ( uPAR ) receives the signal and activates the transcription factor Stat 1 that , in turn , mediates the antiproliferative effects . ^^^ These results provide the first evidence that monocytes signal VSMCs by mechanisms involving the fibrinolytic system , and they imply an important link between the uPA / uPAR related signaling machinery and human vascular disease . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) receptors ( uPAR ) can be engaged for activation signaling either by aggregation or by binding exogenous uPA . ^^^ Human neutrophil uPAR was cross linked or stimulated with uPA after pretreatment with the lipid raft disrupting agents , methyl beta cyclodextrin or filipin 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) binds to its receptor , uPAR , on the surface of cancer cells , leading to the formation of plasmin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) play an important role in cell guidance and chemotaxis during normal and pathological events . uPAR is GPI anchored and the mechanism by which it transmits intracellular polarity cues across the plasma membrane during directional sensing has not been elucidated . ^^^ The constitutively recycling endocytic receptor Endo 180 forms a trimolecular complex with uPAR in the presence of uPA , hence its alternate name uPAR associated protein . ^^^ From these studies , we conclude that Endo 180 is a crucial link between uPA uPAR and setting of the internal cellular compass . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of antisense uPAR and antisense uPA from a bicistronic adenoviral construct inhibits glioma cell invasion , tumor growth , and angiogenesis . ^^^ Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) play an important role in the invasiveness of gliomas and other infiltrative tumors . ^^^ In glioma cell lines and tumors , high grade correlates with increased expression of uPAR and uPA . ^^^ We report here the downregulation of uPAR and uPA by delivery of antisense sequences of uPAR and uPA in a single adenoviral vector , Ad uPAR uPA ( Ad , adenovirus ) . ^^^ The bicistronic construct ( Ad uPAR uPA ) infected glioblastoma cell line had significantly reduced levels of uPAR , uPA enzymatic activity and immunoreactivity for these proteins when compared to controls . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Recently , a recombinant bifunctional inhibitor ( chCys uPA 19 31 ) directed against cysteine proteases and the urokinase type plasminogen activator ( uPA ) / plasmin serine protease system was generated by introducing the uPA receptor ( uPAR ) binding site of uPA into chicken cystatin ( chCysWT ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Bifunctional inhibitors are composed of the N terminal domain of either the human matrix metalloproteinase inhibitors TIMP 1 or TIMP 3 and the cysteine protease inhibitor chicken cystatin ( chCysWT ) ; trifunctional inhibitors are composed of N TIMP 1 or 3 and a chicken cystatin variant harboring the uPAR binding site of uPA , chCys uPA 19 31 , which in addition to its inhibitory activity toward cysteine proteases interferes with the interaction of the serine protease uPA with its receptor . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of urokinase type plasminogen activator ( uPA ) to its glycosyl phosphatidyl inositol ( GPI ) anchored receptor ( uPAR ) mediates a variety of functions in terms of vascular homeostasis , inflammation and tissue repair . ^^^ Both uPA and uPAR , as well as their soluble forms detectable in plasma and other body fluids , represent markers of cancer development and metastasis , and they have been recently described as predictors of human immunodeficiency virus ( HIV ) disease progression , independent of CD4+ T cell counts and viremia . ^^^ A direct link between the uPA / uPAR system and HIV infection was earlier proposed in terms of cleavage of gp 120 envelope by uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It is generally thought that SuPAR scavenges uPA and prevents its interaction with membrane anchored uPAR . ^^^ We show that SuPAR has the potential to directly and in a uPA independent manner block the signaling activity of membrane anchored uPAR . ^^^ Whether SuPAR inhibits signaling is cell type specific , depending on the state of the endogenous uPA uPAR signaling system . ^^^ By contrast , in cells with potent autocrine uPA uPAR signaling systems , including MDA MB 231 breast cancer cells and low density lipoprotein receptor related protein 1 deficient murine embryonic fibroblasts , SuPAR substantially decreases ERK activation . ^^^ The mechanism probably involves competitive displacement of membrane anchored uPAR uPA complex from signaling adaptor proteins . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Association of uPA , PAT 1 , and uPAR in nipple aspirate fluid ( NAF ) with breast cancer . ^^^ PURPOSE : Urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor ( PAI 1 ) , and uPA receptor ( uPAR ) are prognostic factors in various cancer types , especially breast cancer . ^^^ We sought to determine ( 1 ) whether uPA , PAI 1 , and uPAR were detectable in breast nipple aspirate fluid ( NAF ) , a physiologic fluid produced by the breast and collected noninvasively , and ( 2 ) the association of these markers in NAF with the presence of breast cancer . ^^^ PATIENTS AND METHODS : One hundred twenty NAF specimens were collected from women with and women without breast cancer . uPA , PAI 1 , and uPAR expression in NAF was measured by enzyme linked immunosorbent assay . ^^^ RESULTS : Median NAF PAI 1 , but not uPA or uPAR , expression was higher in subjects with breast cancer than in those without breast cancer , regardless of whether expression was controlled for total NAF protein level . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The serine protease urokinase type plasminogen activator ( uPA ) , its inhibitor PAI 1 , and its cellular receptor uPA R ( CD 87 ) are of crucial importance during cellular invasion and migration , required for a variety of physio and pathophysiological processes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The mRNAs of urokinase plasminogen activator ( uPA ) and its receptor , uPAR , contain instability determining AU rich elements ( AREs ) in their 3 ' untranslated regions . ^^^ The cellular proteins binding to these RNA sequences ( ARE ( uPA / uPAR ) ) are not known . ^^^ HuR stabilized an ARE ( uPA ) containing RNA substrate in vitro and stabilized in HeLa Tet off cells both endogenous uPA and uPAR mRNAs and a beta globin reporter mRNA containing the ARE ( uPA ) . ^^^ RNAi mediated depletion of HuR in BT 549 and MDA MB 231 cells significantly reduced the steady state levels of endogenous uPA and uPAR mRNAs . ^^^ These results indicate a role for HuR and MK 2 in regulating the expression of uPA and uPAR genes at the posttranscriptional level . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Substantial evidence exists which implicates the urokinase plasminogen activator system [ urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) ] in the neo vascularization , invasion and metastasis of many solid tumors . ^^^ Components of the uPA / uPAR system are differentially expressed or activated on motile cells including invading tumor cells and leukocytes , and migrating endothelial cells . ^^^ Studies performed in vitro have demonstrated the regulation of the expression of uPA and uPAR by growth and differentiation factors as well as by oncogenes . ^^^ In this review , we summarize recent findings on the role of the components of the uPA / uPAR system in angiogenesis , invasiveness and tumor metastasis . ^^^ Recent experimental evidence obtained using inhibitors of uPA and uPAR has validated this system as a therapeutic target for the development of anti angiogenic and anti metastatic therapeutic agents . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Tumor expression of urokinase type plasminogen activator ( uPA ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and uPA receptor ( uPAR ) are breast cancer prognostic factors . ^^^ We determined the association of uPA , PAI 1 , and uPAR levels in NAF with breast cancer ( 1 ) detection and ( 2 ) advanced disease . ^^^ METHODS : A total of 88 NAF specimens were collected from women with or without breast cancer , and uPA , PAI 1 , and uPAR expression were measured by enzyme linked immunosorbent assay . ^^^ RESULTS : uPA and uPAR were independent predictors of cancer presence ; uPAR was also an independent predictor of advanced disease stage . ^^^ CONCLUSIONS : NAF evaluation of uPA , uPAR , and , perhaps , PAI 1 ( significant only in univariate analysis ) may provide useful breast cancer diagnostic and prognostic information . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : In inflammation , urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) play an important role in fibrinolysis and in activation and chemotaxis of neutrophils and lymphocytes . ^^^ Moreover , the uPA / uPAR system is involved in processes that affect turnover of the extracellular matrix ( ECM ) . ^^^ The aim of this study was to determine the local and systemic release of uPAR , and the expression of uPA and uPAR in renal tissues during acute renal allograft rejection . ^^^ Immunostaining and in situ hybridization for uPA and uPAR were performed on renal biopsies . ^^^ Immunostaining and in situ hybridization showed an up regulation of both uPA and uPAR in rejection biopsies . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition to the proteolytic activity of uPA , which degrades the extracellular matrix , uPA also binds to its receptor ( uPAR ) and controls cell adhesion and migration through the reorganization of actin cytoskeleton . ^^^ Furthermore , aspirin inhibited migration of PC 3 cells , suggesting an effect on the uPA uPAR signaling complex . ^^^ Altogether , our data suggests that aspirin inhibits the formation of uPA uPAR FN alpha3beta1 and uPA uPAR VN alphavbeta 3 complexes , resulting in the suppression of cell adhesion and cell motility of the highly invasive prostate cancer cells PC 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In REC , captopril upregulated the pro survival proteins mortalin 2 , uPA , and uPAR while downregulating the anti growth sprouty 4 and tPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have therefore investigated by immunohistochemistry : ( a ) frequency of uPA expression and its receptor uPAR and the site of synthesis of uPA by in situ hybridization ( ISH ) ; ( b ) MMP 9 and its coexpression with uPA ; ( c ) microvessel density as determined by von Willebrand factor staining and its relationship to uPA and MMP 9 expression ; and ( d ) correlation of these parameters with survival . ^^^ EXPERIMENTAL DESIGN : Archival paraffin sections of 27 pancreatic tumors were semiquantitatively investigated by immunohistochemistry using the following antibodies : ( a ) monoclonal antibodies ( MAbs ) uPA ( 1 ) and uPA ( 2 ) ( 3689 and 394 , respectively ) ; ( b ) MAb uPAR , ( no . 3932 ) ; ( c ) MAb MMP 9 ( no . 936 ) ; and ( d ) rabbit anti F8RA / vWF . ^^^ RESULTS : Both uPA antibodies revealed overexpression of uPA ( 93 % ) often with uniform staining of tumor cells . uPAR and MMP 9 showed focal staining in only 52 and 37 % of tumors , respectively . ^^^ Patients with overexpression of uPA , uPAR , or MMP 9 had a trend toward poorer survival than those who did not express it . ^^^ Microvessel density did not show any significant relationship with uPA , uPAR , and MMP 9 expression and survival . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : The authors found previously that plasma levels of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) were elevated in patients with bladder carcinoma and were associated with features of biologically aggressive disease . ^^^ In the current study , they tested the hypothesis that elevated urinary levels of uPA and uPAR would predict the presence of bladder malignancy by comparing the performance of uPA and uPAR with the performance of bladder wash out cytology in the noninvasive diagnosis of bladder tumors . ^^^ METHODS : An enzyme linked immunosorbent assay was used to compare levels of uPA and uPAR in urine that was collected before cystoscopy from 122 patients with bladder carcinoma and from 107 participants in a control group . ^^^ RESULTS : Urinary levels of uPA and uPAR were higher in patients with bladder carcinoma compared with levels in the control group ( P < 0 . 001 and P = 0 . 016 , respectively ) . ^^^ After controlling for cytology ( odds ratio [ OR ] , 10 . 182 ; 95 % confidence interval [ 95 % CI ] , 4 . 451 23 . 291 ; P < 0 . 001 ) , uPAR ( P for trend = 0 . 168 ) , and age ( P = 0 . 091 ) , those in the highest quartile for uPA had an increased risk of bladder carcinoma compared with those in the lowest quartile ( OR , 3 . 022 ; 95 % CI , 1 . 295 7 . 054 ; P for trend = 0 . 031 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The molecular role of the uPA receptor ( uPAR ) is well characterized with its participation in cell migration and extracellular matrix ( ECM ) degradation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In contrast , TGF beta 1 triggered a large decrease of uPA and tPA , as well as a decrease of uPA and uPAR mRNAs . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of uPA with its receptor ( uPAR ) initiates a proteolytic cascade that results in the conversion of plasminogen to plasmin . ^^^ Over expression of uPA or uPAR is a feature of malignancy and is correlated with tumor progression and metastasis . ^^^ Strategies that target uPA or its receptor with the aim of disrupting the interaction between the two or the ligand independent actions of uPAR include antisense technology , monoclonal antibodies , cytotoxic antibiotics , and synthetic inhibitors of uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
While uPA bound to uPAR independently of its membrane localization and dimerization status , uPA induced uPAR cleavage was strongly accelerated in lipid rafts . ^^^ In contrast to uPA , the binding of Vn occurred preferentially to raft associated dimeric uPAR and was completely blocked by cholesterol depletion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PURPOSE : We have previously reported that urinary urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) are elevated in patients with bladder cancer . ^^^ In the current study we tested the hypothesis that urinary uPA and uPAR would add to the predictive ability of urinary nuclear matrix protein 22 ( NMP 22 ) and cytology for the diagnosis of bladder cancer . ^^^ MATERIALS AND METHODS : Urinary uPA , uPAR and NMP 22 were measured in voided specimens obtained before cystoscopy in 229 consecutive subjects at risk for transitional cell carcinoma ( TCC ) , of whom 122 ( 53 % ) were found to have bladder TCC . ^^^ RESULTS : Urinary uPA , uPAR and NMP 22 were higher in patients with TCC than in controls ( p < 0 . 001 , 0 . 016 and < 0 . 001 , respectively ) , while uPA ( test for trend p = 0 . 018 ) was associated with the risk of TCC after adjusting for NMP 22 ( p = 0 . 028 ) , urinary cytology ( p < 0 . 001 ) , age ( p = 0 . 107 ) and uPAR ( test for trend p = 0 . 756 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To measure the urokinase type plasminogen activator ( UPA ) and its receptor ( UPAR ) in the plasma of patients with cerebral infarction and to study the effects of UPA and UPAR on cerebral infarction . ^^^ METHODS : ELISA sandwich method was used to measure the plasma levels of UPA and UPAR in 89 patients with acute cerebral infarction , subdivided into mild , moderate and severe subgroups according to the modified Edinburgh Scandinavia stroke scale ( mESSS ) , and 30 patients with other disease and 30 healthy persons as controls . ^^^ Two weeks after the onset of stroke , the plasma UPA level was ( 1 185 . 5 + / 384 . 6 ) ng / L , not significantly different from those of the 2 control groups ( both P > 0 . 05 ) ; while the plasma UPAR level in the cerebral infarction was ( 1 159 . 3 + / 261 . 2 ) ng / L , significantly higher than those in the 2 control groups ( P < 0 . 01 ) . ^^^ In addition , the plasma UPA and UPAR levels of the patients who died from cerebral infarction at last were the highest among all the groups . ^^^ CONCLUSION : The plasma levels pf UPA and UPAR increase in patients with cerebral infarction and may be related with the severity of disease . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) , its cell bound receptor ( uPAR ) and its main inhibitor plasminogen activator type 1 ( PAI 1 ) are present primarily in stromal cells in invasive breast carcinoma . ^^^ Breast carcinoma slices ( 30 cases ) , obtained using the Krumdieck tissue slicer , cultured for 48 h in the presence or absence of 100 nM vitamin D 3 , were embedded in formalin fixed paraffin . uPA , uPAR , PAI 1 and VD 3 receptor ( VDR ) were analyzed by immunohistochemistry , and their expression , detected in tumor cells and fibroblasts of the specimens , was not statistically changed by culture conditions . ^^^ The proportion of cases expressing uPA , uPAR and PAI 1 was not affected by VD 3 in epithelial cells , but the fraction of cases displaying strong PAI 1 reactivity in fibroblasts was reduced ( P=0 . 016 ) compared with control slices . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We hypothesize that keloids will have increased staining percentage for uPA and its receptor ( uPAR ) compared with normal scars . ^^^ CONCLUSION : Our observation suggests that the uPA system is involved in the expansion of keloids beyond the wound margins in part through the degradation of the extracellular matrix , a finding that is supported by the strong expression of uPAR in the extracellular matrix and collagenous cords in most keloids studied . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
After VEGF A treatment , the pre existing iris vasculature showed increased permeability , hypertrophy , and activation , as demonstrated by increased staining of CD 31 , PAL E , tPA , uPA , uPAR , Glut 1 , and alphavbeta 3 and alphavbeta 5 integrins , VEGF receptors VEGFR 1 , 2 and 3 , and Tie 2 in endothelial cells , and of NG 2 proteoglycan , uPA , uPAR , integrins and VEGFR 1 in pericytes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The putative uPAR uPAR interaction sites are different from the previously identified uPA binding sites . ^^^ Functionally , peptides uPAR ( 84 95 ) and uPAR ( 240 248 ) could partially inhibit differentiated human U 937 monocyte adhesion to vitronectin in the presence of uPA , indicating that these two uPAR regions might be involved not only in uPAR uPAR but also in uPAR vitronectin interactions . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The authors recently demonstrated that Ganoderma lucidum inhibits constitutively active transcription factors nuclear factor kappa B ( NF kappaB ) and AP 1 , which resulted in the inhibition of expression of urokinase type plasminogen activator ( uPA ) and its receptor uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In acute inflammatory condition , little is known about the expression of the urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in the gastric fibroblasts . ^^^ To clarify the role of human gastric fibroblasts in acute inflammatory conditions such as gastric ulcer , the effects of interleukin ( IL ) 1beta and tumor necrosis factor ( TNF ) alpha on the expression of uPA and uPAR , which were suggested to be associated with tissue remodeling , in gastric fibroblasts were investigated . ^^^ The effect of indomethacin on uPA and uPAR expression in these cells was also examined . ^^^ Furthermore , we investigated the role of prostaglandin E 2 ( PGE 2 ) , which is suggested to play major roles in acute inflammation of the stomatch , on uPA and uPAR expression in gastric fibroblasts . ^^^ The expression level of uPAR mRNA and the amount of uPA antigen on cell surfaces increased in a dose dependent manner on treatment with PGE 2 ( 10 and 50 ng / ml ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The EGFR has been recently described to play a transduction role of uPAR stimuli , mediating uPA induced proliferation in highly malignant cells that overexpress uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These results suggest that kringle domain alone is sufficient for potent anti angiogenic activity and additional growth factor like domain diverts this molecule in undergoing different mechanism such as inhibition of uPA / uPAR interaction rather than undergoing distinct anti angiogenic mechanism driven by kringle domain . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase plasminogen activator ( uPA ) system consists of the serine protease uPA , its glycolipid anchored receptor , uPAR and its 2 serpin inhibitors , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Plasmin , the pivotal thrombolytic enzyme , is generated on the surface of many cell types , where urokinase receptor ( uPAR ) bound urokinase ( uPA ) activates cell bound plasminogen ( Plg ) . ^^^ It has been reported that neutrophils mediate endogenous thrombolysis involving a uPA dependent mechanism , and we previously demonstrated that both uPAR and integrin alpha ( M ) beta ( 2 ) recognize uPA to control cell migration and adhesion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A Kunitz type protease inhibitor , bikunin , downregulates expression of uPA and its receptor uPAR at the mRNA and protein levels in several types of tumor cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHOD : We studied urokinase ( uPA ) , tissue type plasminogen activator ( tPA ) , urokinase receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) expression by in situ hybridization and by immunohistochemistry in 14 NF 2 and 15 sporadic patients with 34 schwannomas . uPAR and vitronectin immunohistochemistry were also studied . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVES : To measure the plasma levels of urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) , and study the relationship between the plasma levels of uPA , PAI 1 and the serum albumin ( Alb ) , collagen type 4 ( CIV ) , the serum hyaluronic acid ( HA ) , prothrombin time ( PT ) and prothrombin activity ( PTA ) in patients with different stages of liver cirrhosis following chronic hepatitis B . ^^^ The plasma levels of uPA , uPAR , PAI 1 and the serum levels of HA , CIV were detected by ELISA . ^^^ RESULTS : With the progression of hepatic fibrosis , the plasma levels of uPA , uPAR and PAI 1 were ( 1 . 36+ / 0 . 43 ) microg / L , ( 3 . 03+ / 1 . 48 ) microg / L and ( 24 . 09+ / 7 . 14 ) microg / L respectively in group A , ( 1 . 79+ / 0 . 62 ) microg / L , ( 4 . 80+ / 2 . 22 ) microg / L and ( 41 . 40+ / 17 . 52 ) microg / L respectively in group B . ^^^ CONCLUSION : In the late of liver cirrhosis , increased PAI 1 together with uPA , uPAR are associated with overall inhibition of matrix degradation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In situ localization of mRNA for the fibrinolytic factors uPA , PAI 1 and uPAR in endometriotic and endometrial tissue . ^^^ The aim of the present study was to localize the uPA , PAI 1 and urokinase plasminogen activator receptor ( uPAR ) mRNA in endometriotic tissue and in endometrium both from women with and without endometriosis . ^^^ With in situ hybridization , we found that uPA mRNA seems to be up regulated in endometriotic glands and endometrial stroma as well as PAI 1 mRNA in endometriotic and endometrial stroma from women with endometriosis . uPAR mRNA likewise appears to be up regulated in both glands and stroma in endometriotic tissue and in endometrial glands from patients compared to endometrial glands and stroma from healthy women . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To probe into the expression and clinical significance of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in urinary transitional cell carcinoma . ^^^ METHODS : Expression of uPA and uPAR were detected in 50 cases of renal pelvis and ureter carcinoma and 40 cases of bladder cancer immunohistochemically . ^^^ RESULTS : The positive rates of uPA and uPAR were closely correlated to the grade and the stage of urinary transitional cell carcinoma ( r = 0 . 979 , P < 0 . 01 ) , whereas uPA and uPAR were not detected in normal kidney , ureter and bladder tissue . ^^^ CONCLUSION : uPA and uPAR are highly expressed in urinary transitional cell carcinoma and they may be responsible for the tumor invasion and metastasis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) serves as a receptor for urokinase plasminogen activator ( uPA ) and plays a role in invasion and migration of certain immune cells , including NK cells . ^^^ We report , herein , that the binding of uPA to uPAR also activates the MAP kinase signaling cascade . ^^^ These results suggest that signaling initiated by either uPAR binding to uPA or by uPAR clustering may depend on the physical association of uPAR with integrins , a process that may be a prerequisite for NK cell accumulation within established tumor metastases during adoptive therapy . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The uPA / uPAR system played an important role in the observed proteolytic activation . ^^^ When uPA was dissociated from uPAR by acid washing , substantially reduced pericellular proteolysis was found . uPAR negative T47D tumor cells did not express significant levels of substrate proteolysis . ^^^ To provide further evidence for the role of the uPA / uPAR system in pericellular proteolysis , peritoneal macrophages from uPA knock out ( uPA / ) and control ( uPA+ / + ) mice were studied . ^^^ Thus , we have : ( 1 ) . developed a novel methodology to detect pericellular proteolytic function , ( 2 ) . demonstrated focused activation of proteolytic enzymatic activity in several cell types , ( 3 ) . demonstrated its usefulness in real time studies of cell migration , and ( 4 ) . showed that the uPA / uPAR system is an important contributor to focal pericellular proteolysis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To understand alterations to the urokinase system that may occur in progressively metastatic prostate cancer cells , we assessed urokinase plasminogen activator receptor ( uPAR ) expression , in vitro motility towards vitronectin , urokinase plasminogen activator ( uPA ) induced growth and growth factor regulation of uPAR expression in three cell lines PC 3 and two derivatives from secondary metastases , PC 3M and PC 3MM2 . ^^^ DU 145 and Tsu Pr 1 cells were included for comparative purposes . uPAR expression increases with metastatic passage in these cell lines and accompanies increased growth and motility responses in the presence of uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The bikunin therapy produced the significant inhibition in expression of the proteolysis ( uPA and uPAR ) and angiogenesis related molecules ( VEGF and bFGF ) . ^^^ In conclusion , combination therapy with bikunin plus paclitaxel may be an effective way to markedly reduce i . p . tumor growth and ascites in ovarian carcinoma possibly through suppression of uPA , uPAR , VEGF and bFGF expression . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously demonstrated that Ganoderma lucidum down regulated the expression of NF kappaB regulated urokinase plasminogen activator ( uPA ) and uPA receptor ( uPAR ) , which resulted in suppression of cell migration of highly invasive human breast and prostate cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In our study , we evaluated the prognostic significance of the major MMP family such as MMP 3 , MMP 9 , MMP 11 and MT 1 MMP at the mRNA in 44 esophageal squamous cell carcinoma ( ESCC ) that were previously characterized for MMP 7 , MMP 1 and MMP 2 , and their relation to urokinase system ( uPA and uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) in gestational tissues ; Measurements and clinical implications . ^^^ BACKGROUND : Urokinase plasminogen activator ( uPA ) and urokinase plasminogen activator receptor ( uPAR ) are central molecules for uPA / uPAR / plasmin dependent proteolysis , which is thought to play a significant role in the development of pregnancy , as well as its many complications . ^^^ OBJECTIVE : To measure the levels of uPA and uPAR in the placenta and myometrium , as well as in the foetal membranes and amniotic fluid . ^^^ RESULTS : uPA and uPAR concentration in gestational tissues , including amniotic fluid , is 100 200 times higher than in plasma . ^^^ Among tissues , the highest uPA level was found in placenta ( 1 . 32 + / 0 . 48 ng / mg of protein ) , and the highest uPAR level in foetal membranes ( 3 . 33 + / 1 . 20 ng / mg of protein ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) play an important role in extracellular matrix degradation and cell migration in the central nervous system ( CNS ) . ^^^ To investigate the role of the uPA / uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex ( ADC ) , we measured soluble uPAR ( suPAR ) levels in cerebrospinal fluid ( CSF ) and plasma from human immunodeficiency virus ( HIV ) 1 infected patients and controls . ^^^ The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA / uPAR system may contribute to the tissue injury and neuronal damage in this disease . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We now show that the cell surface receptor of the uPA system , the urokinase receptor ( uPAR ) , is redistributed to focal adhesions at the leading edge of endothelial cells in response to VEGF . ^^^ VEGF 165 and VEGF E , both interacting with VEGFR 2 , but not PlGF exclusively stimulating VEGFR 1 , induce within minutes internalization of uPAR via an LDL receptor like molecule , dependent on generation of active uPA and the presence of plasminogen activator inhibitor 1 ( PAI 1 ) . uPAR seems to play a pivotal role in VEGFR 2 induced endothelial cell migration because cleavage of surface uPAR impaired the migratory response of endothelial cells toward VEGF E , but not toward PlGF . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Increased expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) is associated with different pathological conditions . ^^^ To evaluate the involvement of plasminogen in such circumstances , we have taken advantage of transgenic mouse models in which overexpression of uPA and / or uPAR in enamel epithelium , basal epidermis , and hair follicles leads to a pathological phenotype ; uPA transgenic mice have chalky white incisors and , when uPAR is co expressed , develop extensive alopecia , epidermal thickening , and subepidermal blisters . ^^^ These results do not argue in favor of a role for uPAR mediated signaling in our experimental model ; rather , they demonstrate an essential , dose dependent , requirement for plasminogen in uPA mediated tissue alterations . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously reported in a series of papers that a Kunitz type protease inhibitor , bikunin , suppresses up regulation of urokinase type plasminogen activator ( uPA ) and its specific receptor ( uPAR ) expression , phosphorylation of ERK1 / 2 and cancer cell invasion in vitro and peritoneal disseminated metastasis in vivo . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The effect of TSP 1 on uPAR and its ligand , urokinase plasminogen activator ( uPA ) , expression were determined by ELISA . ^^^ To determine the role of uPAR on TSP 1 mediated KB tumor cell invasion , we used the three following different strategies : ( a ) . blocking uPAR or its ligand , uPA , with neutralizing antibodies ; ( b ) . enzymatic cleavage of uPAR with glycosylphosphatidylinositol ( GPI ) specific phospholipase C ; and ( c ) . inhibition of plasminogen binding by using epsilon aminocaproic acid . ^^^ RESULTS : TSP 1 up regulated uPAR and uPA expression 3 and 4 fold , respectively . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , NF kappaB and AP 1 control the expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , and expression of both uPA and uPAR correlates with invasive cancer cell phenotype and poor prognosis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Association of uPA and uPAR expression with invasive behaviors of urinary transitional cell carcinoma ] . ^^^ BACKGROUND & OBJECTIVE : Urokinase type plasminogen activator ( uPA ) / its receptor ( uPAR ) , serine protease system , plays a key role in the degradation of extracellular matrix and basement membranes , and intensifying the tumor invasion . ^^^ The study was designed to investigate the expression of uPA and uPAR in urinary transitional cell carcinoma . ^^^ METHODS : The expression and localization of uPA and uPAR were examined among 50 cases of renal pelvic and ureter carcinoma and 40 cases of bladder cancer using the PicTure ( TM ) current type of immunohistochemical two step method . ^^^ RESULTS : The normal pelvic , ureter , and bladder did not express uPA and uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Up to now , there is no consensus on the contribution of membrane bound UPA and its receptor CD 87 ( UPAR ) to the development of atherosclerosis . ^^^ In this study , we determined comparatively the levels of UPAR and UPAR bound UPA in segments of human coronary and aortic vessels with different degrees of atherosclerotic lesions ( macroscopically normal areas , early atherosclerotic lesions , fibrous and calcified plaques ) . ^^^ However , only 20 25 % of the intimal and 30 50 % of the medial glycosylphosphatidylinositol UPAR was occupied by UPA as determined on a molar basis . ^^^ Whether UPAR ' s excess over cell surface UPA provides an additional role for this receptor in atherogenesis besides UPA mediated proteolysis remains to be elucidated . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : The serine protease urokinase type plasminogen ( uPA ) and its receptor ( uPAR ) appear to have a major function in tumor invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The prognostic value of components of the urokinase type plasminogen activator ( uPA ) system , its receptor uPAR ( CD 87 ) , and plasminogen activator inhibitors PAI 1 and PAI 2 is well established . ^^^ High tumor levels of uPA ( P < 0 . 001 ) , uPAR ( P < 0 . 01 ) , and PAI 1 ( P = 0 . 01 ) were associated with a lower efficacy of tamoxifen therapy . ^^^ High levels of uPA , uPAR , and PAI 1 predicted a shorter progression free survival ( PFS ) on tamoxifen in an analysis of the first 9 months of therapy . ^^^ In conclusion , uPA , uPAR , and PAI 1 , components of the urokinase system , are predictive for the efficacy of tamoxifen therapy in patients treated for recurrent breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase plasminogen activator ( uPA ) system consists of the serine protease uPA , the glycolipid anchored receptor , uPAR , and the 2 serpin inhibitors , plasminogen activator inhibitor 1 ( PAI 1 ) and plasminogen activator inhibitor 2 ( PAI 2 ) . ^^^ Recent findings suggest that uPA , uPAR and PAI 1 play a critical role in cancer invasion and metastasis . ^^^ Consistent with their role in cancer dissemination , high levels of uPA , PAI 1 and uPAR in multiple cancer types correlate with adverse patient outcome . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Leukocytes express both urokinase type plasminogen activator ( uPA ) and the urokinase receptor ( uPAR , CD 87 ) . ^^^ We have shown that neutrophil recruitment to the lung during P . aeruginosa pneumonia is impaired in uPAR deficient ( uPAR / ) mice but is normal in uPA / mice . ^^^ However , both uPA / mice and uPAR / mice have impaired lung clearance of P . aeruginosa compared with wild type ( WT ) mice . ^^^ To determine the role of uPA and uPAR in antibacterial host defense , we compared neutrophil bacterial phagocytosis , respiratory burst , and degranulation among uPA / , uPAR / , and WT mice . ^^^ Neutrophil phagocytosis was significantly diminished comparing uPA / and uPAR / mice with WT mice at all time points . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Differential localization and expression of urokinase plasminogen activator ( uPA ) , its receptor ( uPAR ) , and its inhibitor ( PAI 1 ) mRNA and protein in endometrial tissue during the menstrual cycle . ^^^ The urokinase plasminogen activator ( uPA ) dependent proteolytic cascade as well as ligand activation of the uPA receptor ( uPAR ) is critically involved in physiological as well as pathophysiological aspects of tissue expansion and remodelling . ^^^ Cyclic variation and distribution of uPA , uPAR and plasminogen activator inhibitor 1 ( PAI 1 ) mRNA were examined by in situ hybridization , real time PCR and northern blot in normal endometrium . ^^^ Immunostaining for uPA protein is reduced or undetectable at midcycle , thus coinciding with peak concentration of uPA in the uterine fluid . uPAR mRNA is expressed by epithelial cells in the proliferative phase and by stromal cells in the secretory phase . ^^^ Discordant localization of the mRNA and proteins suggest that uPA is produced by stromal cells , released and bound to epithelial cells in both the proliferative and secretory phases , whereas uPAR is released from the stroma and bound to epithelial cells in the secretory phase . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In line with this , uPAR and uPA levels in both resected tumor tissue and plasma are of independent prognostic significance for patient survival in several types of human cancer . ^^^ As the expression of both uPAR and its cognate protease ligand thus appears to be correlated with tumor malignancy , the uPA uPAR interaction represents an attractive target for the development of either antagonists with possible anti invasive effects or cytotoxic agents with anti tumor effects . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
LRP protein was reduced and extracellular accumulation of urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) proteins were greater in uPAR / cultures . ^^^ Enhanced uPAR / fibroblast proliferation was reversed by a recombinant nonfunctional uPA peptide . ^^^ The density of cell bound fluor uPA was similar between uPAR / and uPAR+ / + fibroblasts ( 78 + / 6 versus 92 + / 16 units ) . ^^^ These data suggest that uPAR deficient kidney fibroblasts express lower levels of its scavenger co receptor LRP , resulting in greater extracellular accumulation of uPA and PAI 1 . ^^^ Enhanced proliferation of uPAR / fibroblasts seems to be mediated by uPA dependent ERK signaling via an alternative urokinase receptor . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Interestingly , uPA production was modulated in parallel , although to a lesser degree , with uPAR in these sublines . ^^^ Up regulation of uPAR significantly increased the invasiveness of the moderately invasive DU 145 parental ( DU 145 P ) cells through Matrigel , but this increased invasiveness was not seen in mice . uPA activity appears to contribute to invasiveness at least through Matrigel , as antibody to uPA or amiloride limited the transmigration . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We conclude that markers such as E cadherin , Sialosyl LeX , laminin , collagen 4 , TSP 1 and MVD are useful prognostic markers , alpha , beta , and gamma catenin , MMP 2 and 9 , uPAR , PD ECGF and Bfgf can be considered potentially useful , while research on CD 44 , MMP 1 and 3 , uPA , cathepsin D and VEGF has proved inconclusive . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the study reported here we examined the expression of plasminogen activator inhibitor 1 ( PAI 1 ) , urokinase type plasminogen activator ( uPA ) , and uPA receptor ( uPAR ) , as well as the relevance of such expression to the production of type 4 collagen , a major component of extracellular matrix , in the renal tissue of rats with streptozotocin induced diabetes . ^^^ Because angiotensin 2 is involved in the synthesis of PAI 1 and uPA , we also examined the effect of benazepril , an angiotensin converting enzyme inhibitor , on the expression of PAI 1 , uPA , and uPAR messenger RNAs ( mRNAs ) and type 4 collagen protein . ^^^ We examined the expression of PAI 1 , uPA , and uPAR mRNAs through the use of in situ hybridization and that of type 4 collagen by means of immunohistochemical methods . ^^^ In control rats , we detected weak signals for PAI 1 , uPA , and uPAR mRNAs in glomeruli . ^^^ Diabetic rats exhibited high levels of expression of PAI 1 , uPA , and uPAR mRNAs and type 4 collagen protein , mainly in mesangial cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : The cell surface receptor ( uPAR ) for urokinase plasminogen activator ( uPA ) is a strong prognostic marker in several types of cancer . uPA cleaves the three domain protein uPAR ( 1 3 ) into two fragments : uPAR ( 1 ) , which contains domain 1 ; and uPAR ( 2 3 ) , which contains domains 2 and 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of this study was to evaluate the expression of urokinase plasminogen activator ( uPA ) , its receptor ( uPAR ) and the plasminogen activator inhibitor type 1 ( PAI 1 ) in human aorta , and to balance them with the stage of atherosclerotic lesion . ^^^ We have shown that uPA and uPAR in normal aorta are mostly expressed by intimal smooth muscle cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) system plays a central role in the blood clot dissolution and tissue plasticity . uPA is a serine protease that is also involved in the metastatic process upon activation and binding to its receptor ( uPAR ) . ^^^ We investigated uPA and uPAR gene expression in 20 human transitional cell carcinomas ( TCC ) of the bladder ( n=19 ) and the renal pelvis ( n=1 ) in comparison with adjacent non malignant tissues . ^^^ We performed mRNA in situ hybridization ( isH ) and immunohistochemical staining . uPA mRNA and uPAR mRNA were present in 95 % ( 19 / 20 ) and 85 % ( 17 / 20 ) of the TCC samples , respectively and significantly higher expressed than in the adjacent normal tissue . uPA mRNA was expressed only in malignant urothelial cells , whereas uPAR mRNA was localized in malignant urothelial cells as well as in surrounding stromal cells . ^^^ There was a statistically significant lower expression of uPA / uPAR protein in adjacent normal tissue . ^^^ There was a statistical trend that higher expression of uPA and uPAR corresponded with tumor stage and grade of TCC . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells ( MVECs ) in the expression of the cell associated urokinase type plasminogen activator ( uPA ) / uPA receptor ( uPAR ) system , which is critical in the angiogenic process . ^^^ The uPA / uPAR system was examined at the protein and messenger RNA levels . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It binds to a specific membrane receptor , uPA receptor ( uPAR ) , and activates plasminogen to form plasmin , which participates in tissue degradation and proteolysis . ^^^ Binding of uPA to its receptor accelerates the activation of uPA from pro uPA , enhancing the activity of the uPA / uPAR cascade . ^^^ METHODS : The expression and distribution of uPA and uPAR were analyzed by immunostaining in 52 neuroblastoma tissues ; at the same time we use the reverse transcriptase polymerase chain reaction ( RT PCR ) for neuroendocrine protein gene products 9 . 5 ( PGP 9 . 5 ) mRNA to detect small numbers of NB cells in the peripheral blood and bone marrow ( BM ) and study the relationship uPA and uPAR to the ability of invasion and metastasis of NB cells . ^^^ To identify risk factors for disease progression , the authors performed a retrospective analysis of clinical ( age , sex , and risk group ) and tumor biologic markers ( histology , MYCN , DNA ploidy , chromosome 1 p , PGP9 . 5 , uPA , uPAR , and combined uPA and uPAR ) in all patients . ^^^ RESULTS : The results of immunohistochemistry showed that uPA and uPAR were localized mainly in the membrane and cytoplasm of tumor cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) binds a specific high affinity surface receptor ( uPAR ) . ^^^ The uPA uPAR system is crucial for cell adhesion and migration , and tissue repair . ^^^ We have investigated the presence and function of the uPA uPAR system in human basophils . ^^^ Basophils did not express uPA at either the protein or mRNA level . uPA ( 10 ( 12 ) 10 ( 9 ) M ) and its uPAR binding N terminal fragment ( ATF ) were potent chemoattractants for basophils , but did not induce histamine or cytokine release . ^^^ A polyclonal Ab against uPAR inhibited uPA dependent basophil chemotaxis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have studied the expression of urokinase type plasminogen activator ( uPA ) mRNA , uPA receptor ( uPAR ) mRNA and immunoreactivity , and type 1 plasminogen activator inhibitor ( PAI 1 ) mRNA and immunoreactivity in 16 prostate adenocarcinomas and 9 benign prostate hyperplasias . uPA mRNA and uPAR mRNA expression were found in 9 and 8 of the adenocarcinomas , respectively , and in 7 and 6 of the benign hyperplasias , respectively . ^^^ No immunoreactivity and / or mRNA expression of uPA , uPAR or PAI 1 was observed in cancer cells or in other epithelial cells in any of the cases . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
RT PCR assay for urokinase type plasminogen activator ( uPA ) , its cellular receptor ( uPAR ) , and tumor necrosis factor ( TNF ) alpha was performed to assess the cecal tissue . ^^^ The incidence of abscesses was reduced in all treated groups except the RL group ( P < 0 . 05 ) . uPA , uPAR , and TNF alpha mRNA were highly expressed in the PG+CMC and PL+CMC groups , as compared to the RL group . ^^^ We concluded that the combination of polysaccharides and CMC had significant adhesion and abscess reducing effects compared with their single treatment and the effects may act by modifying the fibrinolytic capacity of uPA , uPAR and TNF alpha produced from activated macrophages in a rat peritonitis model . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The main components in plasminogen activation include plasminogen , tissue plasminogen activator ( tPA ) , urokinase plasminogen activator ( uPA ) , urokinase plasminogen activator receptor ( uPAR ) , and plasminogen activator inhibitors 1 and 2 ( PAI 1 , PAI 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Stable murine macrophage ( Raw264 . 7 ) cell lines expressing high levels of human uPAR , human urokinase plasminogen activator ( uPA ) , or both were established using expression vectors driven by the human CD 68 promoter . ^^^ Stimulation with human uPA specifically induced phosphorylation of early response regulated kinase ( ERK ) in cells expressing human uPAR but not in sham transfected cells . ^^^ The human uPAR expressing Raw264 . 7 cells showed increased adhesion to both human uPA and vitronectin ( Vn ) . ^^^ Raw264 . 7 cells expressing human uPAR or both human uPAR and uPA , but not uPA alone , were detected in the aortic wall of ApoE ( / ) mice , and no cells were detected in that of age matched C57BL / 6J mice after intravenous infusion of the cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) play important physiological functions in extracellular proteolysis , as well as cell adhesion and migration . ^^^ Through dysregulation of these functions , the uPA / uPAR system might be involved in the pathogenesis of AIDS dementia complex ( ADC ) , and , in fact , uPAR has been found to be overexpressed in the cerebrospinal fluid ( CSF ) and brain tissues of patients with ADC . ^^^ In this study , we examined uPAR and uPA expression in the brain of HIV related lesions , as well as CSF levels of soluble uPAR ( suPAR ) , uPA , and complexes between these two molecules ( suPAR / uPA ) in patients with HIV infection with or without ADC . uPAR was highly expressed by macrophages in both HIV encephalitis ( HIV E ) or leukoencephalopathy ( HIV LE ) , with a distribution exceeding that of HIV p 24 antigen . ^^^ Additionally , these findings are consistent with a model in which overexpression of uPAR and overproduction of its soluble form may promote HIV replication via binding and removal of uPA from cell surface . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVES : To determine the role played by the urokinase plasminogen activator ( uPA ) and urokinase plasminogen activator receptor ( uPAR ) system in choroidal neovascularization ( CNV ) and whether inhibition of this system can suppress the extent of CNV in an animal model . ^^^ For 2 weeks following laser treatment , animals were injected intraperitoneally with a novel peptide inhibitor of the uPA uPAR system ( 100 mg / kg twice a day every day , every other day , and once a week ) . ^^^ Systemic administration of the peptide inhibitor of the uPA uPAR system resulted in a significant reduction of CNV ( up to 94 % ) . ^^^ CONCLUSIONS : Our results strongly suggest that up regulation of the uPA uPAR system is an important step during CNV , and significant inhibition of CNV was seen when cell surface associated uPA uPAR activity was prevented with the peptide inhibitor . ^^^ Clinical Relevance Inhibition of the protease system ( uPA uPAR ) may prove to be a potential novel antiangiogenic therapy for CNV as seen in age related macular degeneration . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : The expression of uPA , tPA , urokinase receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and vitronectin was investigated by immunohistochemical staining , in addition to uPA , tPA and PAI 1 expression by in situ hybridization , in samples from eight chronic venous ulcers , five decubitus ulcers , five well granulating acute wounds and five normal skin samples . ^^^ Although no qualitative differences in expression of uPA , PAI 1 or uPAR in the wound edge keratinocytes in chronic ulcers vs . normally granulating wounds were found , their expressions were more pronounced in the granulation tissue of well granulating wounds . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of uPA , one of the fibrinolytic enzymes , its receptor ( uPAR ) and its inhibitor 1 ( PAI 1 ) were also examined . ^^^ The epithelial cells exposed to the air and formed spheroids expressed a larger amount of uPA mRNA than the monolayer , although the amount of uPAR mRNA were comparable in these cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Increased levels of tPA , uPA , uPA receptor ( uPAR ) , and their inhibitor , plasminogen activator inhibitor ( PAI ) 1 , have been found in the cerebrospinal fluid ( CSF ) of patients with bacterial meningitis . ^^^ Here , we show that expression of tPA , uPA , uPAR , PAI 1 , and PAI 2 is up regulated during experimental pneumococcal meningitis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase receptor ( uPAR ) is a key molecule of this system and can bind extracellular and cell membrane molecules such as urokinase ( uPA ) , vitronectin ( VN ) , integrins and chemotaxis receptors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) receptor ( uPAR ) functions in concert with co receptors , including integrins , FPR like receptor 1 / lipoxin A 4 receptor , and the epidermal growth factor receptor ( EGFR ) , to initiate cell signaling . uPAR co receptors may be dynamically organized into a multiprotein signaling receptor complex . ^^^ In Chinese hamster ovary K 1 ( CHO K 1 ) cells , uPA binding to uPAR activates ERK / MAP kinase , even though these cells do not express the EGFR ; however , when CHO K 1 cells are transfected to express the EGFR , ERK activation becomes EGFR dependent . ^^^ We conclude that expression and assembly of uPAR co receptors in a specific cell type determines the response to uPA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
RT PCR assay for urokinase type plasminogen activator ( uPA ) , its cellular receptor ( uPAR ) , tissue type plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI 1 ) , and tumor necrosis factor ( TNF ) alpha was performed to assess the cecal tissue . ^^^ The level of uPA , uPAR , tPA , and TNF alpha was highly expressed in PG and PL group , as compared with the RL group . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Activities ( cath B ( AT ) , cath B ( A7 . 5 ) ) and protein levels of cath B ( C ) , cath L ( C ) , uPA , PAI 1 , uPAR [ measured by three different assays uPAR ( ADI ) , uPAR ( HD 13 ) , uPAR ( IIIF 10 ) ] and TF were measured in homogenates of lung tumour tissue and corresponding non malignant lung parenchyma . ^^^ The concentrations of cath B ( C ) , cath L ( C ) , uPA , PAI 1 , uPAR and TF were determined by ELISAs . uPAR was determined using three different ELISA formats . ^^^ The median levels of cath B ( AT ) ( 5 . 1 fold ) , cath B ( A7 . 5 ) ( 2 . 5 fold ) , cath B ( C ) , ( 8 . 5 fold ) , cath L ( C ) ( 6 . 6 fold ) , uPA ( 6 . 5 fold ) , PAI 1 ( 4 . 2 fold ) , uPAR ( ADI ) ( 2 . 2 fold ) , uPAR ( HD 13 ) ( 4 . 0 fold ) and uPAR ( IIIF 10 ) ( 2 . 6 fold ) were higher in tumour tissue compared to the lung parenchyma . ^^^ PAI 1 significantly correlated with cath B ( AT ) and cath B ( A7 . 5 ) with uPAR ( ADI ) , uPAR ( HD 13 ) , uPAR ( IIIF 10 ) with uPA , and only weakly with TF , but not with cath B ( C ) and cath L ( C ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we established a stable HCT 116 cell line with a gene encoding antisense caveolin 1 ( AS cav 1 ) to examine the effects of caveolin 1 , the main structural protein of caveolae , on the expression and localization of cathepsin B and pro uPA , and their cell surface receptors p 11 and uPA receptor ( uPAR ) , respectively . ^^^ Localization of cathepsin B and pro uPA to caveolae was reduced in AS cav 1 HCT 116 cells , and these cells expressed less total and caveolae associated p 11 and uPAR compared with control cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Immunohistochemical expressions of uPA and its receptor uPAR and their prognostic significant in urinary bladder carcinoma . ^^^ BACKGROUND : The authors found previously that plasma levels of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) were elevated in patients with bladder carcinoma and were associated with features of biologically aggressive disease . ^^^ Paraffin sections of 5 microm thickness were prepared for immunohistochemical staining of uPA and uPAR antigens . ^^^ Thirty six and 46 cases were positive for uPA and uPAR expressions , respectively . ^^^ In univariate analysis , tumor stage , lymph node status , metastases , uPA and uPAR have a significant impact on the survival for these patients . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The presence of tPA , uPA , and urokinase receptor ( uPAR ) in conjunctival tissues were evaluated by immunohistochemistry . uPA , uPAR , and PAI 1 expression and production were measured in conjunctival epithelial cell and fibroblast cultures treated with cytokines . ^^^ Increased staining for uPA and uPAR was found in VKC tissues compared with normal conjunctiva . ^^^ Both conjunctival epithelial cells and fibroblasts demonstrated an increased expression of uPAR after exposure to IL 4 or 13 , whereas uPA was highly expressed by epithelial cells exposed to IL 4 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The interaction of the urokinase type plasminogen activator ( uPA ) receptor ( uPAR ) with integrins plays a critical role in the regulation of cell adhesion and migration . ^^^ We report here that increases in the expression of ganglioside NeuAcalpha 2 > 3Galbeta1 > 3GalNAcbeta1 > 4 ( NeuAcalpha 2 > 8NeuAcalpha2 > 3 ) Galbeta 1 > 4Glcbeta1 Cer ( GT1b ) or NeuAcalpha 2 > 3Galbeta1 > 4Glcbeta1 Cer ( GM 3 ) inhibit uPA dependent cell migration by preventing the association of uPAR with alpha ( 5 ) beta ( 1 ) integrin or uPAR / alpha ( 5 ) beta ( 1 ) integrin with the EGFR , respectively . ^^^ Both gangliosides inhibit uPAR signaling stimulated migration ; however , GM 3 inhibits uPA induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR , whereas GT1b suppresses both uPA induced FAK and EGFR activation by preventing the activation of integrin alpha ( 5 ) beta ( 1 ) . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Thus , the generation of plasmin involves the pro enzyme plasminogen , the urokinase type plasminogen activator uPA and its pro enzyme pro uPA , the uPA inhibitor PAI 1 , the cell surface uPA receptor uPAR , and the plasmin inhibitor alpha ( 2 ) antiplasmin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
E LDL in contrast to n LDL induced substantial activation of the plasminogen activation system as well as of the MMP system in monocytic cells , as measured by enhanced cell surface expression of the urokinase receptor ( uPAR ) , the extracellular matrix metalloproteinase Inducer ( EMMPRIN ) and the membrane type 1 MMPs ( MT 1 MMP , MMP 14 ) , as well as by secretion of active uPA , and of MMP 9 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The serine protease uPA ( urokinase type plasminogen activator ) and its receptor uPAR ( CD 87 ) are often elevated in malignant tumours , hence , inhibition of this tumour associated plasminogen activation system provides an attractive target for therapeutic strategies . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Hypoxia effects : implications for maspin regulation of the uPA / uPAR complex . ^^^ In the April ( 2005 ) issue of Cancer Biology & Therapy , Amir et al report on the novel role maspin plays in the regulation of the urokinase type plasminogen activator ( uPA ) and receptor ( uPAR ) protein system as it relates to hypoxia thereby illustrating yet another potential therapeutic pathway involving maspin . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To determine whether insulinlike growth factor 1 ( IGF 1 ) and hepatocyte growth factor ( HGF ) cooperate to induce migration and invasion of human colorectal carcinoma ( CRC ) cells and whether the effects of IGF 1 and / or HGF are mediated through activation of the urokinase plasminogen activator ( uPA ) / uPA receptor ( uPAR ) system , a central mediator of tumor cell migration and invasion . ^^^ To determine the role of the uPA / uPAR system in IGF 1 induced CRC cell migration and invasion , transwell assays were repeated after pretreating cells with the uPA inhibitor amiloride or with neutralizing antibodies to uPA and uPAR . ^^^ The c Met ribozyme inhibited IGF 1 and HGF mediated migration and invasion , indicating that c Met is essential for these processes . uPA and uPAR inhibition blocked IGF 1 and HGF mediated migration and invasion , suggesting that uPAR is downstream of IGF / IGF IR and HGF / c Met in the signaling pathways that mediate cell migration and invasion . ^^^ CONCLUSIONS : IGF 1 and HGF cooperate to induce migration and invasion of CRC cells , and c Met and uPA / uPAR are required for IGF 1 mediated migration and invasion . ^^^ In our in vitro model of CRC migration and invasion , uPA and uPAR appear to be downstream of IGF IR and c Met and are required for migration and invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The structure was solved at 2 . 7 A in association with a competitive peptide inhibitor of the urokinase type plasminogen activator ( uPA ) uPAR interaction . uPAR is composed of three consecutive three finger domains organized in an almost circular manner , which generates both a deep internal cavity where the peptide binds in a helical conformation , and a large external surface . ^^^ This knowledge combined with the discovery of a convergent binding motif shared by the antagonist peptide and uPA allowed us to build a model of the human uPA uPAR complex . ^^^ This model reveals that the receptor binding module of uPA engages the uPAR central cavity , thus leaving the external receptor surface accessible for other protein interactions ( vitronectin and integrins ) . ^^^ By this unique structural assembly , uPAR can orchestrate the fine interplay with the partners that are required to guide uPA focalized proteolysis on the cell surface and control cell adhesion and migration . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Tumors frequently express urokinase ( uPA ) receptor ( uPAR ) . ^^^ To investigate whether uPAR can efficiently target cancerous cells using amphotropic retroviral vectors , we generated a retrovirus displaying the amino terminal fragment ( ATF ) of uPA as an N terminal extension of viral envelope protein . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Evaluation of cerebrospinal fluid uPA , PAI 1 , and soluble uPAR levels in HIV infected patients . ^^^ To evaluate the potential role of the uPAR / uPA / PAI 1 system in HIV induced blood brain barrier ( BBB ) disruption , CSF uPA dependent plasminogen activation ( PdPA ) was analyzed by casein zymography , and CSF protein levels of all three molecules were measured by ELISA . ^^^ CSF uPAR , but not uPA , PAI 1 , or PdPA levels was significantly increased in neurologically compromised HIV+ patients . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The EGFR has been recently described to play a transduction role of uPAR stimuli , mediating uPA induced proliferation in highly malignant cells that overexpress uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
However , how intracellular signaling is linked to glycolipid anchored uPA receptor ( uPAR ) is unknown . ^^^ We provide evidence that uPAR activation by uPA induces its association with platelet derived growth factor receptor ( PDGFR ) beta . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Saposin C stimulates growth and invasion , activates p42 / 44 and SAPK / JNK signaling pathways of MAPK and upregulates uPA / uPAR expression in prostate cancer and stromal cells . ^^^ Aim : To determine the effect of saposin C ( a known trophic domain of prosaposin ) on proliferation , migration and invasion , as well as its effect on the expression of urokinase plasmonogen activator ( uPA ) , its receptor ( uPAR ) and matrix metalloproteinases ( MMP ) 2 and 9 in normal and malignant prostate cells . ^^^ Results : Saposin C , in a cell type specific manner , upregulates uPA / uPAR and immediate early gene c Jun expression , stimulates cell proliferation , migration and invasion and activates p42 / 44 and SAPK / JNK MAPK pathways in prostate stromal and cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we show that in MCs , the urokinase type plasminogen activator ( uPA ) induces , via its specific receptor ( uPAR , CD 87 ) , upregulated expression of the complement anaphylatoxin C5a receptor ( C5aR , CD 88 ) , and modulates C5a dependent functional responses . ^^^ This effect is mediated via the interaction of the uPA specific receptor ( uPAR , CD 87 ) and gp 130 , a signal transducing subunit of the receptor complexes for the IL 6 cytokine family . ^^^ The data suggest a novel role for uPA / uPAR in glomeruli associated renal failure via a signaling cross talk between the fibrinolytic and immune systems . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
One proteolytic system involved in these processes is the urokinase type plasminogen activator ( uPA ) system , which consists of uPA , uPA receptor ( uPAR ) and uPA inhibitors 1 and 2 ( PAI 1 and PAI 2 ) . ^^^ Increased levels of uPA , PAI 1 and uPAR have been reported to be associated with poor prognosis in patients with breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasminogen activator ( PA ) system comprises the 2 serine proteases , urokinase PA ( uPA ) and tissue PA ( tPA ) , the 2 serpin inhibitors , PAI 1 and PAI 2 and the uPA receptor ( uPAR ; CD 87 ) . ^^^ High levels of uPA , PAI 1 , uPA PAI 1 complex and uPAR in breast cancer tissue are associated with poor prognosis , while high levels of tPA or PAI 2 correlate with good prognosis . ^^^ In this study , pre operative plasma levels of uPA , PAI 1 , uPAR , tPA , uPA PAI 1 complex , and tPA PAI 1 complex were measured in patients with benign ( n=103 ) and malignant breast disease ( n=113 ) by immunoenzymatic assays ( ELISA ) . ^^^ While plasma antigen levels of uPA , PAI 1 , uPA PAI 1 complex and uPAR were not significantly different in the 2 groups , antigen levels of tPA and tPA PAI 1 complex were significantly higher in patients with breast carcinoma compared to the control group . ^^^ In plasma from the breast cancer patients , uPA levels correlated weakly but significantly with those of tPA ( r=0 . 20 , p=0 . 035 ) and uPAR ( r=0 . 208 , p=0 . 028 ) . tPA levels correlated strongly with tPA PAI 1 complex ( r=0 . 972 , p=0 . 0001 ) while uPA PAI 1 levels were significantly associated with PAI 1 levels ( r=0 . 534 , p < 0 . 0001 ) , tPA levels ( r=0 . 348 , p=0 . 0003 ) and tPA PAI 1 levels ( r=0 . 356 , p=0 . 002 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition , As2O3 inhibited migration and invasion of HT 1080 cells stimulated with phorbol 12 myristate 13 aceate ( PMA ) , and suppressed the expression of MMP 2 , 9 , membrane type 1 MMP , uPA , and uPA receptor ( uPAR ) . ^^^ These results suggest that As2O3 inhibits tumor cell invasion by modulating the MMPs / TIMPs and uPA / uPAR / PAI systems of extracellular matrix ( ECM ) degradation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
VEC null cells also present an altered fibrinolytic activity with increases in tPA , uPA , uPAR and a strong reduction in PAI 1 , which may be correlated to the high incidence of abrupt hemorrhages in VEC null tumors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cell associated fibrinolytic system ( urokinase type plasminogen activator , uPA ; uPA receptor , uPAR ; plasminogen activator inhibitor type 1 , PAI 1 ) is pivotal in cell invasion and proliferation . ^^^ METHODS : In SF obtained from RA patients and control subjects , uPA , uPAR and PAI 1 were measured by ELISA of cell lysates and culture medium and by RT PCR of mRNAs . uPA was also studied by zymography . ^^^ RESULTS : RA SF over express uPAR and PAI 1 and are more prone than the normal counterpart to spontaneous and uPA challenged invasion and proliferation , which are counteracted by antagonists of the fibrinolytic system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The interaction between the urokinase receptor ( uPAR ) and its ligand urokinase ( uPA ) mediates phenomena such as tissue remodelling , chemotaxis , tumour invasion , dissemination , proliferation , and angiogenesis . ^^^ The broad spectrum of biological processes that the uPA / uPAR interaction plays a role in has led researchers to speculate that this interaction may be a useful molecular target for therapeutic intervention in several pathological conditions , particularly in the prevention and inhibition of the dissemination of cancer cells . ^^^ In syngeneic and xenograft murine tumour models , in which metastasis is driven by the uPA / uPAR interaction , inhibition of primary tumour growth , metastasis and angiogenesis has been shown with several proteins acting as uPAR antagonists . ^^^ Immunohistochemistry , in conjunction with prognostic studies , has implicated the uPA / uPAR interaction in the dissemination of tumours , such as malignant melanoma , colon cancer , non small cell lung cancer ( NSCLC ) and stomach cancer , as well as breast and ovarian carcinomas . ^^^ A potential inhibitor of the uPA / uPAR interaction should result in a significant increase in the disease free interval and survival time following resection of the primary tumour in a clinical Minimal Residual Disease ( MRD ) setting . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : Extracellular fibrinolysis , controlled by the cell associated fibrinolytic system ( urokinase plasminogen activator , uPA ; uPA receptor , uPAR ; plasminogen activator inhibitor type 1 , PAI 1 ) , is involved in cartilage damage generation and in rheumatoid arthritis ( RA ) synovitis . ^^^ Since steroids reduce the rate of radiological progression of RA , we planned to evaluate in healthy and RA synoviocytes the effects of the steroid deflazacort on uPA , uPAR and PAI 1 expression , and subsequent phenotypic modifications in terms of uPA / uPAR dependent invasion and proliferation . ^^^ METHODS : uPA , uPAR and PAI 1 levels were studied by ELISA , RT PCR ( uPAR ) and zymography ( uPA ) in synoviocytes from four RA patients and four healthy controls . ^^^ Both invasion and proliferation were measured upon treatment with deflazacort 5 muM with or without parallel stimulation with uPA 500 ng / ml or in the presence of monoclonal anti uPA and anti uPAR antibodies . ^^^ Both deflazacort and monoclonal antibodies against uPA and uPAR reduced expression and activity of the system , thus inhibiting invasion and proliferation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition , uPA receptor ( uPAR ) and plasminogen activator inhibitors ( PAIs ) , composed of PAI 1 and 2 , are also known to affect such activities . ^^^ The expression of uPA , uPAR , PAI 1 and PAI 2 was determined by immunohistochemistry . ^^^ RESULTS : The mean immunoreactive scores ( range 0 to 6 ) of uPA , uPAR , PAI 1 and PAI 2 were 3 . 09 , 2 . 22 , 1 . 99 and 0 . 56 , respectively . ^^^ The expression of uPA , uPAR and PAI 1 but not PAI 2 correlated negatively with cause specific survival . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( uPA ) receptor ( uPAR ) has been implicated in signal transduction and biological processes including cancer metastasis , angiogenesis , cell migration , and wound healing . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Serial blood specimens were obtained for pharmacokinetics and levels of urokinase plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma ( RCC ) specimens in comparison with adjacent non malignant renal tissues . mRNA in situ hybridisation and immunohistochemical staining were performed . mRNA of uPA and uPAR was significantly higher expressed in 56 % ( 10 / 18 ) and 72 % ( 13 / 18 ) of the RCC specimens in comparison to the adjacent non malignant renal tissue ( p < 0 . 0001 ) , respectively . uPA mRNA and uPAR mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells . ^^^ The elevated expression of uPAR protein in RCC reached statistical significance compared to adjacent normal tissue ( p=0 . 007 ) . uPAR genes were higher expressed in comparison to uPA alone . ^^^ There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC . ^^^ Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype . ^^^ We conclude that uPA and uPAR are overexpressed in RCC and could function as tumour markers . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In eighty seven patients with CRC , the levels of IL 8 , and VEGF as representative angiogenic factors and urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , plasminogen activator inhibitor 1 ( PAI 1 ) , and PAI 2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues . ^^^ The IL 8 level was significantly associated with tumor size , depth of infiltration , Dukes stage , and liver metastasis , and also significantly correlated with the levels of VEGF , uPAR , uPA , and PAI 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The inhibitory effect of antibody to uPA receptor ( uPAR ) on PAI 1 induced TGF beta function suggested that uPAR mediated the cellular effect of PAI 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To clarify the role of H . pylori infection in the processes of destruction of the extracellular matrix and basement membrane in cancerous tissue , the effect of H . pylori on the expressions of uPA , uPAR and PAI 1 in cancer cells was investigated . ^^^ The specific inductions of uPA , uPAR and PAI 1 mRNA were examined by reverse transcription polymerase chain reaction ( RT PCR ) amplification . ^^^ To evaluate the role of transcription factor NF kappaB in uPA and uPAR gene transcription with H . pylori stimulation , the effect of NF kappaB inhibitor MG 132 on H . pylori induced uPA and uPAR mRNA expression was examined . ^^^ RESULTS : The expressions of both uPA and uPAR mRNAs in the gastric cancer cell lines ( MKN 45 and KATO 3 ) were increased markedly ( uPA mRNA ; MKN 45 : 12 fold , KATO 3 : 5 fold ) ( uPAR mRNA ; MKN 45 : 3 fold , KATO 3 : 3 fold ) with H . pylori NCTC 11637 strain stimulation , whereas the expression levels of uPA and uPAR mRNA did not increase with cagA negative strain stimulation . ^^^ H . pylori induced uPA and uPAR mRNA expressions were strongly down regulated by pretreatment with MG 132 in both cell lines . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , when tyrosine phosphorylation or urokinase type plasminogen activator ( uPA ) / uPAR function was inhibited , both keratinocyte migration and p16INK4a expression were reduced . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Maspin regulates hypoxia mediated stimulation of uPA / uPAR complex in invasive breast cancer cells . ^^^ In this study , we investigated the effect of maspin on the regulation of hypoxia induced expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , with respect to invasive potential in metastatic breast cells MDA MB 231 . ^^^ We hypothesized that maspin can neutralize or mitigate hypoxia induced expression of uPA / uPAR in metastatic breast cancer cells , resulting in suppression of their invasive potential . ^^^ To test our hypothesis , we employed the highly invasive MDA MB 231 breast cancer cells that are devoid of maspin , and transfected them with the maspin gene , and then determined the effect of hypoxia on uPA / uPAR expression . ^^^ Our findings demonstrate that maspin downregulated the basal and hypoxia induced uPA / uPAR expression and reduced the stimulatory effect of hypoxia on the in vitro invasive ability of MDA MB 231 cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) mediated signaling have been implicated in tumor cell invasion , survival , and metastasis in a variety of cancers . ^^^ This study was undertaken to investigate the biological roles of uPA and uPAR in prostate cancer cell invasion and survival , and the potential of uPA and uPAR as targets for prostate cancer therapy . uPA and uPAR expression correlates with the metastatic potential of prostate cancer cells . ^^^ Thus , therapies designed to inhibit uPA and uPAR expression would be beneficial . ^^^ In this study we utilized small hairpin RNAs ( shRNAs ) , also referred to as small interfering RNAs , to target human uPA and uPAR . ^^^ These small interfering RNA constructs significantly inhibited uPA and uPAR expression at both the mRNA and protein levels in the highly metastatic prostate cancer cell line PC 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
There have been reports of strong correlations between poor prognosis in various cancers and concomitant expression of urokinase type plasminogen activator ( uPA ) and its surface receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Pancreatic carcinomas express high levels of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) , both of which mediate cell migration and invasion . ^^^ We investigated the hypotheses that ( a ) insulin like growth factor 1 ( IGF 1 ) and hepatocyte growth factor ( HGF ) mediated migration and invasion of human pancreatic carcinoma cells require uPA and uPAR function and ( b ) inhibition of uPAR inhibits tumor growth , retroperitoneal invasion , and hepatic metastasis of human pancreatic carcinomas in mice . ^^^ We measured the induction of uPA and uPAR following treatment of cells with IGF 1 and HGF using immunoprecipitation and Western blot analysis . ^^^ The importance of uPA and uPAR on L3 . 6pl cell migration and invasion was studied by inhibiting their activities with amiloride and antibodies before cytokine treatment . ^^^ In addition , IGF 1 and HGF induced uPA and uPAR expression in L3 . 6pl cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Accordingly , both uPA dependent enhancement of uPAR expression and cell migration were strongly reduced in transfected cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
IC induced inflammation is mediated by inflammatory cell infiltration , a process highly regulated by the cell surface specific receptor ( uPAR ) , a binding partner for the urokinase type plasminogen activator ( uPA ) . ^^^ We assessed the role of the uPA / uPAR system in IC induced inflammation using the pulmonary reverse passive Arthus reaction in mice lacking uPA and uPAR compared with their corresponding wild type controls . ^^^ Both uPA deficient C57BL / 6J ( uPA ( / ) ) and uPAR deficient mice on a mixed C57BL / 6J ( 75 % ) 10 129 ( 25 % ) background ( uPAR ( / ) ) demonstrated a marked reduction of the inflammatory response due to decreased production of proinflammatory mediators TNF alpha and Glu Leu Arg ( ELR ) CXC chemokine MIP 2 . ^^^ We show that the uPA / uPAR system is activated in lung of wild type mice , particularly in resident alveolar macrophages ( AM ) , early in IC induced alveolitis . ^^^ These data provide the first evidence that the uPA / uPAR plays an important immunoregulatory role in the initiation of the reverse passive Arthus reaction in the lung by setting the threshold for C5a anaphylatoxin receptor / FcgammaR activation on AM . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : The rat model of portal branch ligation ( PBL ) was compared with partial hepatectomy ( PH ) and sham operation ( SO ) and evaluated for the expression of heat shock protein 70 ( hsp 70 ) , heme oxygenase 1 ( hmox 1 ) , early growth response gene 1 ( Egr 1 ) and urokinase type plasminogen activator ( uPA ) , its inhibitor ( PAI 1 ) and receptor ( uPAR ) . ^^^ PAI 1 specific mRNA was transiently elevated at 3 48 h after PBL in the atrophying lobes , whereas uPA and uPAR were unaffected in comparison with PH or SO . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The overexpression of proteases , such as urokinase type plasminogen activator ( uPA ) , its receptor ( uPAR ) , and matrix metalloproteinases ( MMP ) , is correlated with the progression of lung cancer . ^^^ In summary , adenovirus mediated inhibition of uPA uPAR interaction and MMP 9 on the cell surface may be a promising anti invasion and antimetastatic strategy for cancer gene therapy . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expressions and clinical significance of urokinase type activator ( uPA ) and uPA receptor ( uPAR ) in laryngeal squamous cell carcinoma ] . ^^^ OBJECTIVE : To study the expressions and clinical significance of urokinase type plasminogen activator ( uPA ) and uPA receptor ( uPAR ) in laryngeal squamous cell carcinoma ( LSCC ) . ^^^ METHOD : The expressions of uPA and uPAR at protein level were examined in 50 cases of LSCC and 10 cases of normal peripheral tissues around cancer ( as control ) by strep avidin biotin complex ( SABC ) immunohistochemical technique . ^^^ The relationship between the expressions of uPA and uPAR was evaluated by the Spearman ' s rank correlation test . ^^^ Pearson ' s chi square test was used to analyze the relationship between uPA , uPAR and cervical lymph node status . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These results demonstrate the strong anticancer activity of ATF even when its uPAR binding affinity has been suppressed , and indicate that ATF 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 independent interaction via the kringle domain . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Levels of sputum interleukin ( IL ) 8 , IL 10 , interferon ( IFN ) gamma , tumor necrosis factor ( TNF ) alpha , human cationic antimicrobial protein 18 ( CAP 18 ) , urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) , and plasminogen activator inhibitor ( PAI ) 1 were determined . ^^^ CAP 18 levels were elevated in CF and COPD patients compared to control subjects , while asthma patients had reduced CAP 18 levels . uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients , while PAI 1 levels were elevated in all three disease groups . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : We used OVCAR 3 cells and the following methods : cell migration assay , time lapse video microscopy , real time PCR , assays for cellular binding of 125I uPA and cellular degradation of 125I uPA : PAI 1 complex , biosynthetic labeling using 35S methionin , Western blot , Northern blot , and ELISAs for uPA , PAI 1 , and uPAR . ^^^ RESULTS : EGF up regulates both protein and mRNA not only for uPAR , but also for the ligand uPA and its inhibitor PAI 1 . ^^^ Both the anti uPAR antibody R 3 , which inhibits binding of uPA , and the EGFR phosphorylation inhibitor Iressa inhibited cell migration in response to uPA as well as to EGF , suggesting that EGFR and uPAR are engaged in the same multiprotein assembly on the cell surface . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
An uncleavable uPAR mutant allows dissection of signaling pathways in uPA dependent cell migration . ^^^ Urokinase type plasminogen activator ( uPA ) binding to uPAR induces migration , adhesion , and proliferation through multiple interactions with G proteins coupled receptor FPRL 1 , integrins , or the epidermal growth factor ( EGF ) receptor ( EGFR ) . ^^^ We have exploited an uPAR mutant ( hcr , human cleavage resistant ) to dissect the pathways involved in uPA induced cell migration . ^^^ Both wild type ( wt ) and hcr uPAR are able to mediate uPA induced migration , are constitutively associated with the EGFR , and associate with alpha3beta1 integrin upon uPA binding . ^^^ However , they engage different pathways in response to uPA . wt uPAR requires both integrins and FPRL 1 to mediate uPA induced migration , and association of wt uPAR to alpha3beta1 results in uPAR cleavage and extracellular signal regulated kinase ( ERK ) activation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The increased levels of urokinase type plasminogen activator ( uPA ) , uPA receptor ( uPAR ) and type 1 PA inhibitor ( PAI 1 ) are reported in human renal cell carcinoma ( RCC ) . ^^^ In this study , we examined the effect of expression of Cx 32 gene on the production of uPA , uPAR and PAI 1 , and on the induction of PAI 1 stimulated by hypoxia in a human metastatic RCC cell line , Caki 1 cells . ^^^ Cx 32 expression decreased both mRNA level and production of PAI 1 , uPA and uPAR in Caki 1 cells . ^^^ PP 1 , a Src inhibitor , significantly decreased PAI 1 , uPA , uPAR and HIF alpha mRNA levels in Caki 1 cells . ^^^ These results suggest that Cx 32 might reduce PAI 1 , uPA and uPAR production in metastatic RCC cells via the inhibition of Src dependent induction of HIF 1alpha and HIF 2alpha gene expression and that Cx 32 might suppress hypoxia inducible gene expression under hypoxic conditions . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In R 5182 the insert consisted of a 23 residue sequence encoding the uPA binding domain for the urokinase plaminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of the study was to assess the expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in neointima of polyester vascular grafts . ^^^ Immunohistochemistry was performed for uPA and uPAR . ^^^ Graft neointima in dogs was positively stained for uPA with increased intensity at 4 and 12 months , whereas uPAR expression appeared at 4 and its intensity was increased at 12 months . ^^^ Intensive uPA and positive uPAR labeling was shown in human grafts . ^^^ The results demonstrated that in the early period of the healing process of polyester vascular grafts only uPA is present in the neointima in the region of the graft to adjacent artery anastomosis , whereas in healed grafts in dogs and humans uPAR is found as well . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MATERIALS AND METHODS : MB 49 murine bladder cancer cells were cultured in media supplemented with resveratrol , rutin , morin , quercetin , gallic acid and tannic acid ( all of them are polyphenols usually present in Mediterranean diet ) for periods of 24 , 48 and 72 hours to quantify the expression of urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) in the culture medium , as well as of metalloproteinase 9 ( MMP 9 ) and cell proliferation . ^^^ The cells in the media supplemented with the nutrients to study did not show inhibition of mRNA expression of urokinase type plasminogen activator ( uPA ) or its high affinity receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We analyzed cDNA expression by using the CNIO OncoChipTM , a cDNA microarray containing a total of 6386 genes represented by 7237 clones . uPA , uPAr , tPA , PAI 1 and PAI 2 were also studied at RNA and protein levels . ^^^ Microarrays of cDNA expression , RT PCR and Western blot performed in IMR 90 E1A expressing cells showed downregulation of uPA , uPAr , tPA , PAI 1 and upregulation of PAI 2 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Since tumor metastasis requires degradation of the extracellular matrix by the serine protease urokinase type plasminogen activator ( uPA ) , we examined the role of LIMK 1 in the regulation of uPA / uPAR system . ^^^ LIMK 1 overexpression in breast cancer cells upregulated the uPA system , increased uPA promoter activity , induced uPA and uPAR mRNA and protein expression and induced uPA secretion . ^^^ Blocking antibodies against uPA and uPAR suppressed LIMK 1 induced cell invasiveness . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Downregulation of 2 molecules , such as uPA and uPAR , uPAR and MMP 9 , or Cathepsin B and MMP 9 , are more effective to inhibit angiogenesis rather than downregulation of single molecules . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The components of the plasminogen activator ( PA ) system ( urokinase type PA , uPA ; PA inhibitors , PAI 1 / 2 ; uPA receptor , uPAR ) have been implicated in the local degradation of the extracellular matrix ( ECM ) and PCa progression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study examined the ability of IFNgamma and TNFalpha to stimulate a better invasiveness in B 16 murine melanoma cells , and investigated whether this enhanced ability was related to a higher expression of protease activities , such as urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) , and matrix metalloproteinases 2 and 9 ( MMP 2 , MMP 9 ) . ^^^ The invasive phenotype of murine melanoma cells stimulated with IFNgamma and TNFalpha was characterized by an enhanced uPA / uPAR and MMP 9 expression : TNFalpha promoted MMP 9 mRNA expression and pro MMP 9 protein secretion , and the costimulation with IFNgamma and TNFalpha was required to potentiate the expression of mRNA and protein for uPAR , and to induce a redistribution of uPA from the soluble to the cell body associated form . ^^^ These results indicate that invasiveness in B 16 murine melanoma cells can be regulated in a cytokine specific fashion and is dependent on the synergism between the uPA / uPAR system and MMP 9 . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we evaluated uPA , uPAR , and activated ERK levels under hypoxic conditions , and the modulatory effects of iNOS and NO in the MDA MB 231 human breast cancer cell line . ^^^ Cells were incubated in a hypoxic or normoxic incubator and treated with PD 98059 ( a MEK 1 / 2 inhibitor , which abrogates ERK phosphorylation ) and aminoguanidine ( a selective iNOS inhibitor ) . uPAR expression , ERK phosphorylation , and uPA activity were found to be increased under hypoxic conditions . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PURPOSE : The urokinase plasminogen activator ( uPA ) and its receptor ( uPAR ) are expressed by pancreatic cancer cells and can be targeted by the plasminogen activator inhibitor type 2 ( PAI 2 ) . ^^^ METHODS AND MATERIALS : The expression of uPA / uPAR on pancreatic cell lines , human pancreatic cancer tissues , lymph node metastases , and mouse xenografts were detected by immunohistochemistry , confocal microscopy , and flow cytometry . ^^^ RESULTS : uPA / uPAR is strongly expressed on pancreatic cancer cell lines and cancer tissues . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
For cellular invasive processes during a variety of physio and pathophysiological events , including cancer , a fine tuned balance between the formation and loosening of cell adhesive contacts has to occur , implicating the action of pericellular proteases ; among those , the serine protease , urokinase type plasminogen activator ( uPA ) , its inhibitor PAI 1 , and its cellular receptor uPA R ( CD 87 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Among other proteolytic factors , it includes the serine protease urokinase type plasminogen activator ( uPA ) and its three domain ( D1D2D3 ) receptor uPAR ( CD 87 ) , which focuses plasminogen activation to the cell surface . ^^^ The function of uPAR is regulated in part through shedding of domain D 1 by proteases , e . g . , uPA itself or plasmin . ^^^ Here we demonstrate that uPAR is also a target for hK 4 , being cleaved in the D 1 D2 linker sequence and , to a lesser extent , in its D 3 juxtamembrane domain . hK 4 may thus modulate the tumor associated uPA / uPAR system activity by either activating the pro enzyme form of uPA or cleaving the cell surface associated uPA receptor . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Squamous cell carcinoma of the oral cavity is characterized by persistent , disorganized expression of integrin alpha3beta1 and enhanced production of urinary type plasminogen activator ( uPA ) and its receptor ( uPAR ) relative to normal oral mucosa . ^^^ Because multivalent aggregation of alpha3beta1 integrin up regulates uPA and induces a dramatic co clustering of uPAR , we explored the hypothesis that lateral ligation of alpha3beta1 integrin by uPAR contributes to uPA regulation in oral mucosal cells . ^^^ To investigate mechanisms by which uPAR / alpha3beta1 binding enhances uPA expression , integrin dependent signal activation was assessed . ^^^ Proteinase up regulation occurred at the transcriptional level and mutation of the AP 1 ( 1967 ) site in the uPA promoter blocked the uPAR / integrin mediated transcriptional activation . ^^^ Because uPAR is redistributed to clustered alpha3beta1 integrins , the requirement for uPAR / alpha3beta1 interaction in uPA regulation was assessed . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Significant inhibition of choroidal neovascularization ( CNV ) has been observed when cell surface associated uPA uPAR activity is prevented with a specific inhibitor of this proteinase system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It has been questioned whether there are receptors for urokinase type plasminogen activator ( uPA ) that facilitate plasminogen activation other than the high affinity uPA receptor ( uPAR / CD87 ) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation . uPA also promotes cell adhesion , chemotaxis , and proliferation besides plasminogen activation . ^^^ These uPA induced signaling events are not mediated by uPAR , but mediated by unidentified , lower affinity receptors for the uPA kringle . ^^^ We found that uPA binds specifically to integrin alpha 5 beta 3 on CHO cells depleted of uPAR . ^^^ On CHO cell depleted of uPAR , uPA enhanced plasminogen activation in a kringle and alpha 5 beta 3 dependent manner . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the highly invasive MDA MB 231 cell line , 10 ( 8 ) M CT decreased both uPA and uPAR mRNA and protein expression which was associated with inhibition of the extracellular signal regulated kinase ( ERK ) 1 / 2 pathway . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We hypothesized that : 1 ) macrophage accumulation and cardiac fibrosis in SR uPA+ / o mice are dependent on localization of uPA by the uPA receptor ( uPAR ) ; 2 ) activation of plasminogen by uPA and subsequent activation of transforming growth factor beta 1 ( TGF beta 1 ) and matrix metalloproteinase ( MMP ) 2 and 9 by plasmin are critical pathways through which uPA expressing macrophages accumulate in the heart and cause fibrosis ; and 3 ) uPA induced cardiac fibrosis can be attenuated by treatment with verapamil . ^^^ Our studies revealed that plasminogen is necessary for uPA induced cardiac fibrosis and macrophage accumulation but uPAR is not . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( uPA ) and its receptor ( uPAR ) play a critical role in cell migration and angiogenesis by facilitating proteolysis of extracellular matrix . ^^^ The aim of the present study was to characterize the uPA / uPAR dependent proteolytic potential of EPC outgrown from human umbilical cord blood and to analyze its contribution to their angiogenic properties in vitro . ^^^ Using quantitative flow cytometry , enzyme linked immunosorbent assays and zymography , we demonstrated that EPDC displayed higher levels of uPA and uPAR . ^^^ Moreover , tumor necrosis factor alpha and vascular endothelial growth factor , known to be locally secreted in ischemic areas , further increased the proteolytic potential of EPDC by up regulating uPA and uPAR expression respectively . ^^^ In conclusion , these findings indicated that EPDC are characterized by high intrinsic uPA / uPAR dependent proteolytic potential that could contribute to their invasive and angiogenic behaviour . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We noted that maspin ( a ) colocalized with uPA and uPA receptor ( uPAR ) , ( b ) enhanced the interaction between uPAR and low density lipoprotein receptor related protein , and ( c ) induced rapid internalization of uPA and uPAR . ^^^ The maspin effects on surface associated uPA and uPAR required the interaction between uPA and uPAR . ^^^ These data show an important role of maspin RSL in regulating the uPA / uPAR dependent cell detachment . ^^^ Together , our data led to a new hypothesis that maspin may stabilize mature FACs by quenching localized uPA / uPAR complex before uPA activation . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of the serine protease urokinase ( uPA ) to its receptor ( uPAR ) plays a central role in the molecular events coordinating tumor cell adhesion , migration , and invasion . ^^^ This anti apoptotic effect is retained by a uPA derived synthetic peptide corresponding to the receptor binding domain and is inhibited by anti uPAR polyclonal antibodies . ^^^ Furthermore , the stable reduction of uPA or uPAR expression by RNA interference leads to an increased susceptibility to UV , cisplatin , and detachment induced apoptosis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A monoclonal antibody against human uPA receptor ( uPAR ) , mAb 3936 , inhibited HGF mediated tumor cell invasion in a dose dependent manner . ^^^ CONCLUSIONS : These results suggest that NUGC 3 and MKN 28 cells express functional c Met , which may provide a therapeutic target for interfering with metastases of cancer cells by inhibiting uPA and uPAR mediated proteolysis . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The uPA / uPAR system is involved in tumour progression and metastasis of a variety of cancers . ^^^ Expression of uPA and its receptor ( uPAR ) were localised to the invading front of the tumours . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The high affinity interaction between the serine protease urokinase type plasminogen activator ( uPA ) and its glycolipid anchored receptor ( uPAR ) represents one of the key regulatory steps in cell surface associated plasminogen activation . ^^^ On the basis on our crystal structure solved for uPAR in complex with a peptide antagonist , we recently proposed a model for the corresponding complex with the growth factor like domain of uPA ( Llinas et al . ( 2005 ) EMBO J . 24 , 1655 1663 ) . ^^^ The kinetic rate constants for the interaction between pro uPA and 244 purified uPAR mutants with single site replacements were determined by surface plasmon resonance . ^^^ Mutations causing delta deltaG > or = 1 kcal / mol for the uPA interaction are all located within or at the rim of the central cavity uniquely formed by the assembly of all three domains in uPAR , whereas none are found outside this crevice . ^^^ Identification of specific cross linking sites in uPAR and pro uPA enabled us to build a model of the uPAR 10 uPA complex in which the kringle domain of uPA was positioned by the constraints established by the range of these cross linkers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we used siRNA to simultaneously target urokinase plasminogen activator ( uPA ) and its receptor , uPAR . ^^^ A human CMV promoter driven mammalian expression vector ( pU 2 ) was used to produce hairpin double stranded RNA ( hp RNA ) to target uPA and uPAR . ^^^ As determined by Western blotting and fibrin zymography , pU 2 effectively inhibited uPAR protein levels and uPA enzymatic activity in meningioma cells ( IOMM Lee ) . ^^^ Intratumoral injections of the plasmid vector expressing siRNA for uPA and uPAR resulted in regression of pre established , subcutaneous tumors in mice . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A strong increase of proliferation was absent when the monoclonal anti uPAR antibody IIIF 10 ( blocking uPA binding site ) , soluble uPAR ( scavenger effect ) and phosphatidyl inositol specific phospholipase C ( PI PLC , degrading uPAR ) was added prior to the addition of HMW uPA . ^^^ In conclusion , HMW uPA and ATF induce proliferation of breast cancer cells by binding to uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Nevertheless , no change in cell migration was observed when TKI treated cells were supplied with external uPA , thus indicating more complex mechanisms leading to decreased cell invasion . uPAR expression was measured with an enzyme linked immunosorbent assay ( ELISA ) in PC 3 and DU 145 prostate carcinoma cells treated with the two TKI genistein and AG 1478 . uPAR mRNA levels were measured with real time reverse transcriptase polymerase chain reaction ( RT PCR ) . uPAR immunocytochemistry was used to examine the receptor distribution in cells grown on a reconstituted basal lamina . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Previous reports have shown that genistein and tyrphostin AG 1478 , two tyrosine kinase inhibitors ( TKIs ) , exert multiple cellular effects in prostate carcinoma cells , e . g . a reduction in the production of urokinase plasminogen activator ( uPA ) and its receptor uPAR , and a decrease in the cells ' ability to invade an artificial basement membrane . ^^^ Among the effects of TKIs , a lowered uPA and uPAR transcription was demonstrated in genistein treated cells , while a few metalloproteinases ( MMPs ) were affected . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We hypothesized that increased expression of uPAR and its ligand , uPA , enhance eosinophil adhesion in patients with asthma . ^^^ Patients with allergic asthma underwent segmental bronchoprovocation with allergen ; 48 h later , peripheral blood and airway ( from bronchoalveolar lavage fluid ) eosinophils were isolated . uPA and uPAR protein expression were measured by flow cytometry and Western blot ; mRNA was quantified by real time PCR . ^^^ Airway eosinophils expressed significantly more uPA and uPAR protein and uPAR mRNA than peripheral blood eosinophils . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These results reveal for the first time that the uPA uPAR interaction leads to activation of Stat 3 , independent of its catalytic activity but dependent on its interaction with its receptor , uPAR , leading to DNA synthesis in lung epithelial cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor , microvessel density , progression and survival time of patients with gastric cancer . ^^^ AIM : To investigate the correlations between the expression of urokinase type plasminogen activator ( uPA ) mRNA , uPA receptor ( uPAR ) mRNA and vascular endothelial growth factor ( VEGF ) protein and clinicopathologic features , microvessel density ( MVD ) and survival time . ^^^ METHODS : In situ hybridization and immuno histochemistry techniques were used to study the expressions of uPA mRNA , uPAR mRNA , VEGF and CD 34 protein in 105 gastric carcinoma specimens . ^^^ RESULTS : Expressions of uPA mRNA , uPAR mRNA and VEGF protein were observed in 61 ( 58 . 1 % ) cases , 70 ( 66 . 7 % ) cases and 67 ( 63 . 8 % ) cases , respectively . ^^^ The mean MVD in the specimens positive for the uPA mRNA , uPAR mRNA and VEGF protein was markedly higher than those with negative expression groups . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We also show that alterations in the distribution of VE cadherin and beta catenin occur after IGFII and serum or VN stimulation , and propose that the via VN IGFII effects may be facilitated by interaction of the mannose 6 phosphate / IGFII receptor ( M6P / IGFIIR ) with the urokinase type plasminogen activator receptor ( uPAR ) and its ligand ( uPA ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
UPA , UPAR , ECE 1 , PAFAH1B1 , PGT , INOS , ENOS , TPA , ICAM 1 , VCAM 1 , PAI 1 , PAI 2 , VWF , PTGDR , F 3 , THBD ) , which was most evident after 24 hours . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MMP 2 and MMP 9 levels were examined using gelatin zymography and Western blotting ; their endogenous inhibitors , tissue inhibitor of metalloproteinase 2 ( TIMP 2 ) and tissue inhibitor of metalloproteinase 1 ( TIMP 1 ) , were assessed by Western blotting . uPA , uPAR and PAI 1 were examined using enzyme linked immunosorbent assay ( ELISA ) . ^^^ In rectal tumors , there was an increased activity of uPA compared with the activity in colon tumors ( P = 0 . 0266 ) , however urokinase type plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor 1 ( PAI 1 ) showed no significant difference between colon and rectal cancer tissues . ^^^ CONCLUSION : These findings suggest that uPA may be expressed differentially in colon and rectal cancers , however , the activities or protein levels of MMP 2 , MMP 9 , TIMP 1 , TIMP 2 , PAI 1 and uPAR are not affected by tumor location in the colon or the rectum . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Over expression of uPA in the VTA induces doxycycline dependent expression of its receptor , uPAR , but not its inhibitor , plasminogen activator inhibitor 1 ( PAI 1 ) . uPAR expression in the VTA is repressed upon silencing of uPA with lentiviruses expressing siRNAs . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Assignment of the urokinase type plasminogen activator receptor gene ( PLAUR ) to chromosome 19q13 . 1 q13 . 2 . ^^^ The urokinase type plasminogen activator receptor ( uPAR ) is a key molecule in the regulation of cell surface plasminogen activation and , as such , plays an important role in many normal as well as pathological processes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The specific phosphatase inhibitor , okadaic acid , increases the level of mRNA for the receptor for urokinase type plasminogen activator ( u PAR ) in 8 out of 13 human cell lines . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We report here that the cellular receptor for urokinase type plasminogen activator ( u PAR ) is deficient on affected peripheral blood monocytes and granulocytes from four individuals with PNH as evidenced by chemical cross linking analysis as well as by immunofluorescence flow cytometry using a monoclonal anti u PAR antibody . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using an immortalized human glomerular epithelial cell line ( E 71 A1 ) , we studied the effect of endothelin 1 ( ET 1 ) , a potent vasoconstrictor peptide , on the synthesis of urokinase type plasminogen activator ( u PA ) and its receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( u PAR ) was demonstrated on cultured smooth muscle cells ( SMCs ) of bovine aorta . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Two PstI polymorphisms for the urokinase type plasminogen activator receptor gene ( PLAUR ) . ^^^ The cDNA probe puPAR 2 detects two PstI polymorphisms in the urokinase type plasminogen activator receptor gene ( PLAUR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have compared the cell specific expression and regulation of the receptor for urokinase type plasminogen activator ( u PAR ) by transforming growth factor beta type 1 ( TGF beta 1 ) in 10 human cell lines derived from both normal and neoplastic tissues . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cellular receptor for human urokinase type plasminogen activator ( u PAR ) is shown by several independent criteria to be a true member of a family of integral membrane proteins , anchored to the plasma membrane exclusively by a COOH terminal glycosyl phosphatidylinositol moiety . 1 ) Amino acid analysis of u PAR after micropurification by affinity chromatography and N [ 2 hydroxy 1 , 1 bis ( hydroxymethyl ) ethyl ] glycine sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed the presence of 2 3 mol of ethanolamine / mol protein . 2 ) Membrane bound u PAR is efficiently released from the surface of human U 937 cells by trace amounts of purified bacterial phosphatidylinositol specific phospholipase C . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have studied the effect of the tumor promotor phorbol myristate acetate ( PMA ) on the level of mRNA for the receptor for urokinase type plasminogen activator ( u PAR ) in the human monocyte like cell line U 937 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study in situ hybridization methods were used to examine biopsy samples from 13 adenocarcinomas of the colon for the presence of mRNA for the urokinase type plasminogen activator ( u PA ) and its specific cell surface receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We therefore evaluated the mRNA levels for urokinase type plasminogen activator ( u PA ) , urokinase type plasminogen activator receptor ( u PAR ) , and plasminogen activator inhibitor type 1 ( PAI 1 ) by using Northern blot analysis and in situ hybridization in four cases of GCT and spindle shaped mononuclear cells at the 35th passage from a GCT . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) focuses at the cell surface the activation of pro uPA and , hence , the formation of plasmin , thus enhancing directional extracellular proteolysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The ability of U 937 monocyte like cells and KATO 3 cells ( a human gastric carcinoma line ) to potentiate activation of plasminogen by single chain urokinase type plasminogen activator ( scu PA ) , as mediated by the cell receptor for urokinase ( u PAR ) , was compared . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator ( u PA ) to specific receptors ( u PAR ) on the surface of endothelial cells contributes to the regulation of plasmin dependent processes such as fibrinolysis and angiogenesis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Since the plasminogen activator [ PA / plasminogen activator inhibitor ( PAI ) system is believed to be involved in a breakdown of articular cartilage in osteoarthritis ( OA ) , we studied the modulation of single components of the fibrinolytic system ( urokinase type plasminogen activator , u PA ; plasminogen activator inhibitor 1 , PAI 1 ; the surface receptor for u PA , u PAR ) in human chondrocytes in the presence of piroxicam . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Receptors were labeled using fluorescein , rhodamine , or AMCA conjugated F ( ab ' ) 2 fragments of anti Fc gamma RIIIB ( CD 16 ) , anti CR 3 ( CD11b / CD18 ) , and anti uPAR ( urokinase type plasminogen activator receptor ) antibodies , intact phycoerythrin labeled interleukin 8 , and fluorescein or rhodamine labeled Con A ( concanavalin A ) , Boc PLPLP ( tert butyl oxycarbonyl Phe ( D ) Leu Phe ( D ) Leu Phe OH ) , and N formyl Nle Leu Phe Nle Tyr Lys . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Thrombin induced a rapid ( < 5 minute ) , time ( 0 to 30 minutes ) and dose ( 0 . 1 to 8 U / mL ) dependent decrease in the specific binding of 125I labeled two chain urokinase type plasminogen activator ( tcu PA ) or diisopropylfluoro phosphate tcu PA to urokinase type plasminogen activator receptor ( u PAR ) in cultured ECs from various sources ( range , 21 % to 50 % ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of the receptor for the urokinase type plasminogen activator ( uPAR ) has been studied by flow cytometry and immunohistology in normal blood and bone marrow cells , in vitro activated lymphoid cells , and tissue samples from reactive lymph nodes ( n = 6 ) , thymus ( n = 2 ) and malignant lymphomas ( n = 82 ) , or leukemias ( n = 32 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Since vascular smooth muscle cell ( SMC ) migration may be an important event in atherosclerosis and in intimal thickening after vascular injury , we studied the cell surface expression of a receptor for urokinase type plasminogen activator ( u PAR ) in cultured human vascular SMC . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The murine urokinase type plasminogen activator receptor ( uPAR ) gene has been isolated and its complete nucleotide sequence established . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Bovine vascular smooth muscle cells ( SMC ) express the urokinase type plasminogen activator receptor ( u PAR ) claimed to be important in cell invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cellular receptor for urokinase type plasminogen activator ( uPAR ) is a glycosylphosphatidylinositol ( GPI ) anchored membrane protein that plays a central role in pericellular plasminogen activation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We studied urokinase type plasminogen activator ( u PA ) dependent chemotaxis and DNA synthesis in both human fibroblasts and LB 6 mouse fibroblasts transfected with human u PA receptor ( u PAR ) gene ( LB 6 clone 19 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study tests the possible physical interactions of another extensively glycosylated glycosyl phosphatidylinositol linked protein , the urokinase type plasminogen activator receptor ( uPAR ) , with CR 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Paraffin wax embedded specimens from 30 cases of colonic adenocarcinoma were investigated for immunoreactivity for the receptor of urokinase type plasminogen activator ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( u PA ) , its receptor ( u PAR ) , and type 1 inhibitor ( PAI 1 ) in cultured human mesangial cells were investigated . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Full length cDNAs encoding bovine urokinase type plasminogen activator ( u PA ) and urokinase receptor ( u PAR ) were cloned from an aortic endothelial cell cDNA library using PCR amplified cDNA fragments as probes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Histological samples from 60 invasive ductal breast carcinomas were investigated for immunoreactivity for the receptor for urokinase type plasminogen activator ( uPAR ) with the use of two monoclonal antibodies recognizing different epitopes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for human urokinase type plasminogen activator ( uPAR ) is synthesized as a 313 residue long polypeptide containing 28 cysteine residues , the pattern of which defines three homologous repeats within the protein . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( u PA ) or its amino terminal fragment ( ATF ) containing the u PA receptor ( u PAR ) binding domain , is known to promote monocyte adhesion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Previous studies have shown that the leukocyte integrin CR 3 ( CD11b / CD18 ) is physically associated with the urokinase type plasminogen activator receptor ( uPAR ; CD 87 ) , a glycosyl phosphatidylinositol ( GPI ) linked protein , in resting neutrophil membranes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Mice homozygously deficient for the urokinase type plasminogen activator ( u PA ) receptor ( u PAR 1 ) were generated by homologous recombination in D 3 , embryonic stem cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have investigated the localization of urokinase type plasminogen activator ( u PA ) , type 1 plasminogen activator inhibitor ( PAI 1 ) , u PA receptor ( u PAR ) and alpha ( 2 ) macroglobulin receptor / low density lipoprotein receptor related protein ( alpha ( 2 ) MR / LRP ) in human breast tumors by immunohistochemical methods . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To further investigate possible involvement of the PA system , we quantified immunoreactive urokinase type plasminogen activator ( u PA ) , tissue type plasminogen activator ( t PA ) , both plasminogen activator inhibitors ( PAI 1 and PAI 2 ) and u PA receptor ( u PAR ) in synovial tissue extracts of 14 patients with rheumatoid arthritis ( RA ) and 12 with osteoarthritis ( OA ) . u PA , PAI 1 , PAI 2 and u PAR concentrations were significantly higher in RA than in OA patients . t PA antigen levels were significantly lower in RA than in OA synovial tissue extracts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand binding site on uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Thrombin and other mitogens regulate the expression of the urokinase type plasminogen activator receptor ( uPAR ) protein and mRNA levels in bovine vascular smooth muscle cells ( SMC ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Macrophages in the tissues have been shown to express receptor for urokinase type plasminogen activator ( uPAR ) on their cell surface which plays an important role in cell invasion and attachment . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( u PAR ) facilitates extracellular matrix proteolysis by accelerating plasmin formation at the cell surface . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( u PA ) was found to induce monocyte adhesion through a u PA receptor ( u PAR ) mediated cAMP dependent signal transduction pathway ( J . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The level of urokinase type plasminogen activator ( u PA ) receptor ( u PAR ) mRNA increased up to 2 . 2 fold in response to heat shock , which was associated with the increased u PA binding and cell surface u PA activity determined by adding exogenous u PA to acid treated HUVECs . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
By immunocytochemical staining for the urokinase type plasminogen activator receptor ( uPAR ) which is a glycosyl phosphatidyl inositol ( GPI ) anchored protein expressed by normal , but not by PNH affected , neutrophils , it was shown that the uPAR positive subpopulation of normal neutrophils predominated among the faster migrating cells ( 60 80 % normal cells at the front of migration ) while uPAR negative ( i . e . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Treatment of human pleural mesothelioma ( MS 1 ) cells with phorbol myristate acetate ( PMA ) and cycloheximide results in 17 and 10 fold , respectively , increases in steady state expression of urokinase type plasminogen activator receptor ( uPAR ) mRNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator ( u PA ) bound to its receptor , u PAR , initiates signal transduction pathways able to induce expression of the activator protein 1 ( AP 1 ) family member c fos [ 1 ] . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MMP 9 ( gelatinase B ) and urokinase type plasminogen activator receptor ( u PAR ) , which are involved in cancer cell invasion and metastasis , are reported to be predominantly expressed by immune / inflammatory cells in human colorectal cancers . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It is well known that a urokinase type plasminogen activator receptor ( uPAR ) is a key protein in the plasminogen activation system , which plays a proteolytically important role in the invasion and metastasis of various cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The interaction of urokinase type plasminogen activator ( u PA ) or of u PA amino terminal fragment ( u PA ATF ) with the cell surface receptor ( u PAR ) was found to stimulate an increase of glucose uptake in many cell lines , ranging from normal and transformed human fibroblasts , mouse fibroblasts transfected with human u PAR , and cells of epidermal origin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The observed increase in urokinase type plasminogen activator ( u PA ) and its receptor ( u PAR ) in synovial tissue of patients with rheumatoid arthritis ( RA ) suggests pathophysiological involvement of the plasminogen activation ( PA ) system in inflammatory joint disease . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Treatment of isolated Kupffer cells with PI PLC reduced the binding of rscu PA by 40 % , suggesting the involvement of the urokinase type Plasminogen Activator Receptor ( u PAR ) in the recognition of rscu PA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have shown previously that the urokinase type plasminogen activator receptor ( uPAR ) physically associates with beta 2 integrins on human leukocyte membranes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using this approach , the expression of RNAs for tissue type plasminogen activator , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , plasminogen activator inhibitor 2 , protease nexin , and urokinase receptor isoform 1 ( uPAR 1 ) were detected in mouse osteoclasts . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cell surface urokinase type plasminogen activator receptor ( uPAR ) has been shown to be a key molecule in regulating plasminogen mediated extracellular proteolysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of urokinase type plasminogen activator ( u PA ) , its receptor ( u PAR ) and metalloproteases activity were analyzed in 4 human gastric cancer cell lines ( AGS , Hs746T , SNU 1 , and SNU 5 ) , in an attempt to relate these activities to their invasive potential and tumorigenicity on the modified chorioallantoic membranes ( CAM ) of chick embryos . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( u PAR ) facilitates extracellular matrix degradation in part by accelerating plasmin formation at the cell surface . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we investigated the presence of both LRP and urokinase type plasminogen activator receptor ( uPAR ) in astrocytoma tissues and in glioma cell lines by PCR and immunohistochemical analysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase receptor ( uPAR ) binds urokinase type plasminogen activator ( u PA ) through specific interactions with uPAR domain 1 , and vitronectin through interactions with a site within uPAR domains 2 and 3 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Aortic SMC were isolated from transgenic mice showing single inactivations of the t PA , u PA , plasminogen activator inhibitor 1 , or urokinase type plasminogen activator receptor ( u PAR ) genes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present study , the anti apoptotic activity of TGFbeta on cultured vascular smooth muscle cells ( SMC ) isolated from the aorta of transgenic mice with single inactivation of genes encoding the tissue type plasminogen activator ( t PA ( / ) ) , urokinase type plasminogen activator ( u PA ( / ) ) , urokinase receptor ( u PAR ( / ) ) or plasminogen ( Plg ( / ) ) genes was examined . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In human colon carcinomas , urokinase type plasminogen activator ( u PA ) produced by stroma cells can bind to cancer cell associated u PA receptor ( u PAR ) , and then catalyze the conversion of plasminogen ( Pg ) into plasmin ( Pm ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Comparison of the exon intron structure of the PLI 1 gene with those of genes encoding urokinase type plasminogen activator receptor ( uPAR ) , Ly 6 , CD 59 and neurotoxins showed that they have characteristic unit encoding approximately 90 amino acid residues , which is divided over two exons . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Affinity purification of GPI anchored urokinase type plasminogen activator receptor ( uPAR ) from chrysotile exposed cells demonstrated that asbestos altered the profile of proteins and phosphoproteins complexed with this receptor . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It has been proposed that the urokinase receptor ( u PAR ) is essential for the various biological roles of urokinase type plasminogen activator ( u PA ) in vivo , and that smooth muscle cells require u PA for migration during arterial neointima formation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We investigated the effect of dibutyryl cyclic AMP ( Bt 2 cAMP ) on urokinase type plasminogen activator receptor ( uPAR ) expression in human PL 21 myeloid leukemia cells and compared it with the effect of phorbol myristate acetate ( PMA ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Because earlier studies have shown that the receptor for urokinase type plasminogen activator ( uPAR ) may facilitate such events , we studied the effect of hypoxia on the expression of uPAR by first trimester human trophoblasts ( HTR 8 / SVneo ) and human umbilical vein endothelial cells ( HUVEC ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Ascites and serum of patients with ovarian carcinoma contain a soluble form of urokinase type plasminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Matrix metalloproteinase 3 ( MMP 3 , or stromelysin 1 ) specifically hydrolyzes the Glu 143 Leu144 peptide bond in 45 kDa single chain urokinase type plasminogen activator ( scu PA ) and in its two chain ( tcu PA ) derivative , yielding a 17 kDa NH 2 terminal domain comprising the u PA receptor ( u PAR ) binding site and a 32 kDa COOH terminal moiety containing the serine proteinase domain of u PA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Hepatocyte growth factor receptor ( c met ) , autocrine motility factor receptor ( AMFR ) , and urokinase type plasminogen activator receptor ( uPAR ) are known to play important roles in tumor cell migration , invasion , and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Bovine mammary epithelial ( BME UV 1 , clone E T and BME UV , clone E T 2 ) and myoepithelial ( BMM UV , clone m T 2 ) cell lines were used to study the modulation of cell associated activity of urokinase type plasminogen activator ( u PA ) , as well as mRNA transcripts of u PA , its receptor ( u PAR ) , and inhibitors ( PAI 1 and PAI 2 ) during the cell cycle . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using chorio allantoic membranes ( CAMs ) of chick embryos and severe combined immunodeficient ( SCID ) mice , we investigated the effects of urokinase type plasminogen activator receptor ( u PAR ) over expression on the process of invasion and tumorigenicity . ^^^ By the transfection of u PAR cDNA , 3 u PAR over expressing clones expressing 1 . 6 to 4 . 6 fold more u PAR mRNA than parent cells were obtained from a human epidermoid carcinoma cell line , HEp 3 , that expresses urokinase type plasminogen activator ( u PA ) and u PAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A previous study has reported a high frequency of rare alleles of the urokinase type plasminogen activator receptor ( uPAR ) in a set of 15 colorectal cancer ( CRC ) cell lines . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( u PAR ) has been implicated in tumor progression , and previous studies have shown that the expression of this gene is strongly up regulated by PMA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The transmembranous urokinase type plasminogen activator receptor ( uPAR ; CD 87 ) focuses the formation of active plasmin at the cell surface , thus enhancing directional extracellular proteolysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PAR ) and plasminogen activator inhibitor ( PAI ) 1 and 2 was examined in 105 cases of primary lung cancer tissue using immunohistochemical staining and reverse transcriptase polymerase chain reaction ( RT PCR ) techniques . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Human urokinase type plasminogen activator receptor ( uPAR ) is a glycolipid anchored membrane glycoprotein comprising three structurally similar domains . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The tissue concentrations of urokinase type plasminogen activator ( u PA ) , urokinase type plasminogen activator receptor ( u PAR ) , plasminogen activator inhibitor type 1 ( PAI 1 ) and tissue type plasminogen activator ( t PA ) were investigated by an ELISA technique in normal and malignant samples of the prostate from 24 patients undergoing radical prostatectomy for organ confined prostate cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator receptor ( UPA R CD 87 ) is a GPI anchored membrane protein which promotes the generation of plasmin on the surface of many cell types , probably facilitating cellular extravasation and tissue invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Both the urokinase type plasminogen activator receptor ( uPAR ) and the plasminogen activator inhibitor 1 ( PAI 1 ) are thought to be important factors in this system . ^^^ Urokinase type plasminogen activator receptor mRNA , PAI 1 mRNA , uPAR and PAI 1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci . ^^^ Urokinase type plasminogen activator receptor protein expression correlated with lymphatic , venous invasion ( P < 0 . 01 ) and lymph node metastasis ( P < 0 . 05 ) ; uPAR mRNA expression correlated with lymphatic , venous invasion and lymph node metastasis ( P < 0 . 05 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : The urokinase type plasminogen activator receptor ( uPAR ) may play a critical role in cancer invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This protein may prove to be a new member of the family of integrin associated , GPI anchored proteins , which includes urokinase type plasminogen activator receptor ( uPAR ) , lipopolysaccharide ( LPS ) / LPS binding protein ( LBP ) receptor ( CD 14 ) , and Fcgamma receptor IIIB ( CD16b ) ; all of which are regulators of integrin function . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The structural and functional properties of the urokinase type plasminogen activator ( u PA ) that are involved in the mitogenic effect of this proteolytic enzyme on human melanoma cells M 14 and IF 6 and the role of the u PA receptor ( u PAR ) in transducing this signal were analyzed . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression and localization of the urokinase type plasminogen activator receptor ( uPAR ) in the human placenta . ^^^ The urokinase type plasminogen ( uP ) is activated by u PA and urokinase type plasminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression and functional role of urokinase type plasminogen activator receptor ( UPA R ; CD 87 ) in normal and acute leukemia cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Stromal expression of urokinase type plasminogen activator receptor ( uPAR ) is associated with invasive growth in primary liver cancer . ^^^ AIMS / BACKGROUND : Expression of urokinase type plasminogen activator receptor ( uPAR ) was studied in 25 hepatocellular carcinomas ( HCCs ) and seven cholangiocellular carcinomas ( CCCs ) by immunohistochemistry . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study , we investigated the presence of both LRP and urokinase type plasminogen activator receptor ( uPAR ) in glioblastoma by reverse transcriptase polymerase chain reaction ( RT PCR ) , and the cellular localization of LRP in glioblastoma tissues by immunohistochemical analysis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) plays a critical role in the regulation of cell surface plasminogen activation in several physiological and pathological conditions . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
There are four genes affected by beta catenin overexpression ; three overexpressed genes code for two components of the AP 1 transcription complex , c jun and fra 1 , and for the urokinase type plasminogen activator receptor ( uPAR ) , whose transcription is activated by AP 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The sequences of LsPLIgamma A and LsPLIgamma B showed 65 and 74 % homology , respectively , to those of the corresponding subunits of N . naja kaouthia PLIgamma , and had two tandem patterns of cysteine residues , characteristic of the urokinase type plasminogen activator receptor ( uPAR ) and members of the Ly 6 superfamily . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously shown that the glycosylphosphatidyl inositol ( GPI ) linked urokinase type plasminogen activator receptor ( uPAR ) reversibly associates with the integrins complement receptor type 3 ( CR 3 ; alphaMbeta 2 ) and CR 4 ( alphaxbeta 2 ) during leukocyte motility . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Single chain urokinase type plasminogen activator ( scu PA ) possesses enzymatic activity that increases by 2 3 orders of magnitude upon binding to its cellular cofactor , the u PA receptor ( u PAR ) , hence activating an enzymatic cascade initially composed of zymogens . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The catalytically inactive precursor of urokinase type plasminogen activator ( pro u PA ) induced a chemotactic response in rat smooth muscle cells ( RSMC ) through binding to the membrane receptor of urokinase ( u PA receptor [ u PAR ] ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
An 8 . 5 kb 5 ' flanking region of the human urokinase type plasminogen activator receptor ( uPAR ) gene was cloned and the detailed uPAR promoter region defined in an 188 bp fragment between bases 141 and +47 relative to the transcription start site . 5 ' Deletion to 100 and 60 in the region abolished its promoter activity , indicating that an 81 bp segment between 141 and 61 , which contains a proximal AP 1 site at position 70 , is required for uPAR promoter activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To explore the potential of this approach , urokinase type plasminogen activator receptor ( uPAR ) , a membrane protein extensively modified post translationally , was selected . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Therefore , expression analysis performed by Northern blotting and immunohistochemistry were extended to include IFN gamma , the IFN gamma receptor beta subunit ( IFN gammaRbeta ) , three secondary response genes induced by interaction of IFN gamma with IFN gamma receptor complexes , ie , IL 1beta converting enzyme ( ICE ) , intercellular adhesion molecule 1 ( ICAM 1 ) , and urokinase type plasminogen activator receptor ( uPAR ) , and a cytokine inducing IFN gamma expression , ie , interleukin 18 ( IL 18 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Reverse transcription polymerase chain reaction products revealed positive expressions of integrin alpha 5 and beta 1 , urokinase type plasminogen activator receptor ( uPAR ) , vascular endothelial growth factor and nm 23 H1 mRNAs of cell line MHCC 97 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To assess the participation of the plasminogen activation system in the invasiveness of esophageal squamous cell carcinoma , we performed immunohistochemistry and in situ hybridization to study the distribution of a urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PAR ) , and plasminogen activator inhibitor 2 ( PAI 2 ) . u PA and PAI 2 were expressed heterogeneously in cancer cells , and restricted expression was found in stromal cells , especially fibroblasts , that were located in the immediate proximity of the cancerous cells . u PAR was found only in cancer cells located at the periphery of tumors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator receptor ( uPAR ) is known to be involved in conversion of plasminogen into plasmin and its expression can be regulated by a variety of biological agents including transforming growth factor beta ( TGF beta ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase type plasminogen activator ( uPAR ) ( CD 87 ) plays an important role in leukocyte adhesion and migration . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The effects of heat treatment on the viability and fibrinolytic potential of four cultured human carcinoma cell lines , fibrosarcoma cells ( HT 1080 ) , lung adenocarcinoma cells with highly metastatic potential ( HAL 8 ) , melanoma cells ( Bowes ) and osteosarcoma cells ( NY ) , determined by measuring their levels of urokinase type plasminogen activator ( u PA ) and its specific receptor ( u PAR ) , were investigated by comparing them with those of human umbilical vein endothelial cells ( HUVECs ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously defined the promoter of human urokinase type plasminogen activator receptor ( uPAR ) gene in a 188 bp fragment between bases 141 and +47 relative to the translation start site . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Wnt 1 decreased the NGF induced expression of the late response gene SCG 10 but not of the immediate early genes , fos , Nur 77 and UPAR ( urokinase type plasminogen activator receptor ) nor of the late response genes GAP 43 and collagenase . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We previously showed that downregulation of the urokinase type plasminogen activator receptor ( uPAR ) in the SNB 19 human glioblastoma cell line by the stable transfection of a plasmid expressing a 300 bp antisense sequence to the 5 ' end of the uPAR gene produced a decrease in the amount of target mRNA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Glioblastomas express more urokinase type plasminogen activator receptor ( uPAR ) than do low grade gliomas and normal brain tissue . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The distribution of the urokinase type plasminogen activator receptor ( uPAR ) on human glioma cells was examined as a function of culture conditions , using immunofluorescence and immunophotoelectron microscopy . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) exists as a GPI anchored glycoprotein ( Mr=50 60 kDa ) on the surface of various cell types . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Applying a novel , highly specific and sensitive immunoabsorption / Western blotting technique we have identified in vitro in conditioned cell culture medium and in vivo in human urine different soluble forms of the urokinase type plasminogen activator receptor ( uPAR / CD87 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We also investigated the expression of matrix metalloproteinases ( MMPs ) , urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PAR ) and c MET in these cell lines in vitro and in vivo . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Lesion associated expression of urokinase type plasminogen activator receptor ( uPAR , CD 87 ) in human cerebral malaria . ^^^ We have now analyzed expression of urokinase type plasminogen activator receptor ( uPAR , CD 87 ) , which is part of a cell surface associated proteolytic system , in brains of eight CM patients and seven neuropathologically unaltered and diseased controls by immunohistochemistry . ^^^ Recent data provide convincing evidence that the serine protease urokinase type plasminogen activator receptor ( uPAR ) is a key molecule in promoting cell adhesion and spreading . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
On the other hand , there is now good evidence that parts of the fibrinolytic system , such as urokinase type plasminogen activator and its receptor ( `` uPAR ' ' ) , can be used as strong predictors of outcome in several types of cancer , specifically breast cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Human immunodeficiency virus 1 ( HIV 1 ) infection has been shown to result in up regulation of the urokinase type plasminogen activator receptor ( uPAR / CD87 ) on leukocytes in vitro and in vivo . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR , CD 87 ) is a highly glycosylated 55 to 60 kDa protein anchored to the cell membrane through a glycosylphosphatidylinositol moiety that promotes the acquisition of plasmin on the surface of cells and subsequent cell movement and migration by binding urokinase type plasminogen activator . uPAR also occurs in a soluble form in body fluids and tumor extracts , and both membrane and soluble uPAR are overexpressed in patients with tumors . uPAR may be a factor in inflammatory disorders as well . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The murine receptor for urokinase type plasminogen activator is primarily expressed in tissues actively undergoing remodeling . uPAR is a cellular receptor for urokinase plasminogen activator , an enzyme involved in extracellular matrix degradation during processes involving tissue remodeling . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Down regulation of integrin alpha ( 5 ) beta ( 3 ) expression and integrin mediated signaling in glioma cells by adenovirus mediated transfer of antisense urokinase type plasminogen activator receptor ( uPAR ) and sense p 16 genes . ^^^ The expression of urokinase type plasminogen activator receptor ( uPAR ) was recently shown to co regulate with the expression of alpha ( 5 ) beta ( 3 ) integrin . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator up regulates its own expression by endothelial cells and monocytes via the u PAR pathway . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The downregulation of transcriptional AP 1 activity by curcumin as seen in the dual luciferase assay caused inhibition of LLC cell invasion through the repression of expression of the mRNAs for urokinase type plasminogen activator ( u PA ) and its receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Downregulation of urokinase type plasminogen activator receptor ( uPAR ) induces caspase mediated cell death in human glioblastoma cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Plasminogen can be converted to plasmin either via the tissue type plasminogen activator ( t PA ) or via the urokinase type plasminogen activator ( u PA ) / u PA receptor ( u PAR ) pathway . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Our previous studies showed that the urokinase type plasminogen activator receptor ( uPAR ) and the p 16 tumor suppressor gene play a significant role in glioma invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : The plasma level of tissue factor ( TF ) , tissue factor pathway inhibitor ( TFPI ) , thrombin antithrombin complex ( TAT ) , plasmin antiplasmin complex ( PAP ) , urokinase type plasminogen activator ( u PA ) , urokinase type plasminogen activator receptor ( u PAR ) and the TF level of bone marrow blasts lysate were measured by ELISA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Since our discovery of the CR 3 FcgammaRIIIB interaction , the plasma membrane protein repertoire of beta 1 , beta 2 , and beta 3 integrins has grown to include : FcgammaRIIA ( CD 32 ) , uPAR ( urokinase type plasminogen activator receptor ; CD 87 ) , CD 14 , voltage gated K+channels ( Kv1 . 3 ) , integrin associated protein ( IAP ) , CD 98 , tetraspans ( TM4SF ) , insulin receptors , and PDGFbeta receptors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To compare the effects of thrombin on the expression of the tissue factor ( TF ) and urokinase type plasminogen activator receptor ( uPAR ) mRNA in the cultured vascular endothelial cells ( VEC ) and U 937 cell line . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present study demonstrates that hypoxia promotes spontaneous lymph node metastasis in R 18 human melanoma xenografts by up regulating the urokinase type plasminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To investigate the expression levels of the receptor for urokinase type plasminogen activator ( uPAR ) on granulocytes and the soluble uPAR ( suPAR ) level in plasma from patients with paroxysmal nocturnal hemoglobinuria ( PNH ) and its clinical application in the diagnosis of this disorder . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PURPOSE : To study the invasion related molecule urokinase type plasminogen activator receptor ( u PAR ) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Urokinase type plasminogen activator receptor ( uPAR ) plays an important role in cancer invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The direct and indirect contributions of the urokinase type plasminogen activator receptor ( uPAR ) system in inflammatory processes , as they relate to recruitment of leukocytes , define novel functions and could serve as therapeutic targets for related vasculopathies . ^^^ Urokinase type plasminogen activator was identified as a potent mitogen for vascular smooth muscle cells , an observation that was independent of the presence of uPAR and its proteolytic activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A central mechanism for regulating plasmin generation is through the binding of the two plasminogen activators to specific cellular receptors : urokinase type plasminogen activator to the glycolipid anchored membrane protein uPAR , and tissue plasminogen activator to a type 2 transmembrane protein recently identified on vascular smooth muscle cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor for urokinase type plasminogen activator ( uPAR ) also is attached to the cell membrane by a GPI anchor , and that soluble uPAR ( suPAR ) is present in plasma . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator ( u PA ) receptor ( u PAR ) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia simulated increase of vessel permeability . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) is a multifunctional molecule involved in migration and adhesion of leukocytes to sites of inflammation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Decreased expression of intercellular adhesion molecule 1 ( ICAM 1 ) and urokinase type plasminogen activator receptor ( uPAR ) is associated with tumor cell spreading in vivo . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Previous studies showed that beta ( 3 ) integrins regulate expression of the urokinase type plasminogen activator receptor ( uPAR ) through outside in signalling involving the cytoplasmic domain . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The objective of this study was to evaluate the role of plakoglobin in the pathogenesis of acantholysis in pemphigus vulgaris ( PV ) and its relation with the urokinase type plasminogen activator receptor ( uPAR ) expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The low density lipoprotein receptor related protein ( LRP 1 ) binds and mediates the endocytosis of multiple ligands , transports the urokinase type plasminogen activator receptor ( uPAR ) and other membrane proteins into endosomes , and binds intracellular adaptor proteins involved in cell signaling . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator and its receptor ( u PAR ) contribute to prostate cancer metastases by promoting extracellular matrix degradation and growth factor activation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A 15 mer asODNs targeted against the translation start site of UPAR ( urokinase type plasminogen activator receptor ) mRNA were introduced into CCL 229 cells by lipid mediated DNA transfection and the variation of the levels of uPAR mRNA , uPAR antigen expression of the levels of uPAR mRNA , uPAR antigen expression on the cell sruface and invasion properties were observed by reverse transcription polymerase chain reaction ( RT PCR ) , flowcytometry ( FCM ) and aminion invasion assay , the morphological feature of the cell after asODNs treatment was observed by scanning electron microscope ( SEM ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator and its receptor ( uPAR ) have an important role in tumor invasion and metastasis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase type plasminogen activator receptor ( uPAR ) to the mannose 6 phosphate / insulin like growth factor 2 receptor : contrasting interactions of full length and soluble forms of uPAR . ^^^ Urokinase type plasminogen activator receptor ( uPAR ) binding by the mannose 6 phosphate / insulin like growth factor 2 receptor ( Man 6 P / IGF2R ) is considered important to Man 6 P / IGF2R tumor suppressor function via regulation of cell surface proteolytic activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cellular receptor for urokinase type plasminogen activator , uPAR , plays a central role in both cell surface associated proteolysis and cellular adhesion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To establish an introductory understanding of the quantitative mRNA expression of MT SP 1 and to correlate these levels with urokinase type plasminogen activator receptor ( uPAR ) , a key component of extracellular proteolysis , quantitative RT PCR was carried out . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator receptor ( uPAR ) is attached to cell membranes by a glycosylphosphatidylinositol ( GPI ) anchor , and as such is devoid of an intracellular domain , but is nevertheless able to initiate signal transduction . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We investigated the effect of HGF on the invasion of PC 3 and DU 145 prostate cancer cells through a reconstituted basement membrane ( Matrigel ) , the haptotactic migration to fibronectin substrate , the expression of protein and mRNA for matrix metalloproteinases ( MMP ) 1 and 9 , membrane type 1 MMP ( MT 1 MMP ) , urokinase type plasminogen activator ( u PA ) and its receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study gives the first clinical evidence that urokinase type plasminogen activator receptor ( u PAR ) gene expression is tumor specifically regulated via an activator protein ( AP ) 2 / Sp1 promoter element in a large patient subpopulation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The prognostic value of the soluble urokinase type plasminogen activator receptor ( s uPAR ) in plasma of breast cancer patients with and without metastatic disease . ^^^ Elevated levels of soluble uPAR ( s uPAR ) and other fibrinolytic parameters functionally related to the urokinase type plasminogen activator system might indicate the presence of cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( u PAR ) contributes to cell migration and proteolysis in normal and cancerous tissues . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This depression of RhoA activity is necessary to permit a second ERK dependent signaling event via uPAR , the receptor for urokinase type plasminogen activator , to activate Rac and to drive motility through polarized lamellipodia extension . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The down regulation of transcriptional anti activator protein 1 ( AP 1 ) activity by TAC 101 paralleled the inhibition of cell invasion and migration through the repression of expression of the mRNAs for urokinase type plasminogen activator ( u PA ) and its receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here we provide evidence that PGE 2 transactivates c Met R ( contingent upon functional EGFR ) , increases tyrosine phosphorylation and nuclear accumulation of beta catenin , and induces urokinase type plasminogen activator receptor ( uPAR ) mRNA expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR , CD 87 ) plays a central role in the plasminogen activation cascade , which participates in extracellular matrix degradation , cell migration and invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Previous studies have indicated that the receptor for urokinase type plasminogen activator , uPAR , can form functional complexes with integrin receptors thereby modulating integrin activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The aim of this work was to evaluate by immunohistochemistry ( IHC ) the expression of both LRP 1 and urokinase type plasminogen activator receptor ( uPAR ) at different developmental stages of rat prostate disease by using a prostate cancer model previously developed in our laboratory . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A recombinant fusion protein targeting the urokinase type plasminogen activator receptor ( uPAR ) and delivering a potent catalytic toxin has the advantage of simultaneously targeting both over expressed uPAR on glioblastoma cells and on the tumor neovasculature . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
CD 87 ( urokinase type plasminogen activator receptor ) , function and pathology in hematological disorders : a review . ^^^ The analysis of CD 87 ( urokinase type plasminogen activator receptor uPAR ) expression has a potential role in the diagnostic or prognostic work up of several hematological malignancies , particularly acute leukemia and multiple myeloma . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) plays a critical role in cartilage degradation during osteoarthritis as it regulates pericellular proteolysis mediated by serine proteinases . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Overexpression of urokinase type plasminogen activator receptor ( uPAR ) on tumor cell surface is essential for invasion and metastasis in a variety of tumor cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Pimonidazole was used as a hypoxia marker , and hypoxia and urokinase type plasminogen activator receptor ( uPAR ) expression were detected by immunohistochemistry . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , some of the GPI 80 on pseudopodia of migrating neutrophils during the late phase was associated with urokinase type plasminogen activator receptor ( uPAR ) , a regulator of beta 2 integrin dependent adherence and migration . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) is involved in cell migration and tissue remodelling , as a receptor for pro uPA , as a cell adhesion component , and in a soluble form as a chemoattractant . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here , we show that LRP1B , a member of LRs , modulates the migration of smooth muscle cells ( SMCs ) by increasing the degradation of membrane receptors , urokinase type plasminogen activator receptor ( uPAR ) , and platelet derived growth factor receptor ( PDGFR ) beta . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
AIM : To investigate the relationship of urokinase type plasminogen activator receptor ( uPAR ) and vascular endothelial growth factor ( VEGF ) expression with clinical and pathological characteristics of human gallbladder cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Moreover , AdCC cell lines expressed higher surface levels of urokinase type plasminogen activator receptor ( uPAR ) than did SCC cell lines . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Increases in cell size and shape correlate with over expression of two integrins and the urokinase type plasminogen activator receptor ( uPAR ) , which is also involved in cell adhesion and is often over expressed in metastatic cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Real time quantitative PCR determination of urokinase type plasminogen activator receptor ( uPAR ) expression of isolated micrometastatic cells from bone marrow of breast cancer patients . ^^^ Urokinase type plasminogen activator receptor ( uPAR ) was quantified by real time quantitative RT PCR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using amide hydrogen exchange combined with electrospray ionization mass spectrometry , we have in this study determined the number of amide hydrogens on several peptides that become solvent inaccessible as a result of their high affinity interaction with the urokinase type plasminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) and tumor necrosis factor ( TNF ) alpha mRNA were highly expressed in PG0 . 25 , 0 . 5 , PL0 . 25 , and 0 . 5 groups . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Leucocyte expression of the urokinase receptor [ urokinase type plasminogen activator receptor ( uPAR ) ] is regulated by inflammatory mediators . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We investigated the involvement of the urokinase type plasminogen activator receptor ( uPAR ) in granulocyte colony stimulating factor ( G CSF ) induced mobilization of CD34+ hematopoietic stem cells ( HSCs ) from 16 healthy donors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Based on earlier studies , we hypothesized that metastasis was governed primarily by the proangiogenic factor interleukin 8 ( IL 8 ) in D 12 tumors and by the invasive growth promoting receptor urokinase type plasminogen activator receptor ( uPAR ) in R 18 tumors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Four tumour markers for urinary bladder cancer tissue polypeptide antigen ( TPA ) , HER 2 / neu ( ERB B 2 ) , urokinase type plasminogen activator receptor ( uPAR ) and TP 53 mutation . ^^^ The urokinase type plasminogen activator receptor ( uPAR ) is a GPI linked single chain glycoprotein . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously demonstrated the effectiveness of adenovirus mediated expression of antisense urokinase type plasminogen activator receptor ( uPAR ) and matrix metalloproteinase 9 ( MMP 9 ) in inhibiting tumor invasion in vitro and ex vivo . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In addition , in hr sMTf treated HMEC 1 , the expression of both urokinase type plasminogen activator receptor ( u PAR ) and low density lipoprotein receptor related protein ( LRP ) are down regulated . ^^^ However , fluorescence activated cell sorting analysis revealed a 25 % increase in cell surface u PAR in hr sMTf treated HMEC 1 , whereas the binding of the urokinase type plasminogen activator ( u PA ) * plasminogen activator inhibitor 1 ( PAI 1 ) complex is decreased . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase type plasminogen activator receptor ( UPA R ; CD 87 ) is a membrane protein responsible for plasmin expression on cells facilitating cellular extravasations and tissue invasions . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This study investigated whether the release of urokinase type plasminogen activator receptor ( uPAR ) in whole blood cultures was affected by HIV infection . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase type plasminogen activator receptor ( uPAR ) sustains cell migration through its capacity to promote pericellular proteolysis , regulate integrin function , and mediate chemotactic signaling in response to urokinase . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Expression of urokinase type plasminogen activator receptor ( uPAR ) in primary central nervous system neoplasms . ^^^ The cellular receptor for urokinase type plasminogen activator receptor ( uPAR ) is a member of the glycosylphosphatidylinositol ( GPI ) anchored protein family . ^^^ It is a specific cell surface receptor for its ligand , urokinase type plasminogen activator , which catalyzes the formation of plasmin from plasminogen to generate the proteolytic cascade and leads to the breakdown of the extracellular matrix . uPAR has been shown to correlate with a propensity to tumor invasion and metastasis in several types of non central nervous system tumors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Here we show that HOXA 3 increases endothelial cell migration , induces angiogenesis in vivo , and leads to increased expression of the matrix metalloproteinase 14 ( MMP 14 ) and urokinase type plasminogen activator receptor ( uPAR ) genes in endothelial cells in culture and in vivo in response to injury . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Posttranscriptional regulation of urokinase type plasminogen activator receptor ( uPAR ) mRNA involves the interaction of a uPAR mRNA coding region sequence with phosphoglycerate kinase ( PGK ) , a 50 kDa uPAR mRNA binding protein . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have previously shown that in adult mice with a null mutation in the urokinase type plasminogen activator receptor ( uPAR ) gene , maintained on a C57BL / 6J / 129Sv background , there is a selective loss of GABAergic interneurons in anterior cingulate and parietal cortex , with the parvalbumin expressing subpopulation preferentially affected . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore Serp 1 has demonstrated the capacity to utilize a mammalian serine protease receptor , the urokinase type plasminogen activator receptor ( uPAR ) , to alter cellular signaling in part through the actin binding protein cytoskeletal system ( via filamin B ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In the present study , we report activation of TGF beta by functional and physical co operation of the mannose 6 phosphate / insulin like growth factor 2 receptor ( CD 222 ) and the urokinase type plasminogen activator receptor ( CD 87 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
It has been shown previously that increased levels of urokinase type plasminogen activator receptor ( uPAR ) correlate well with higher invasive phenotype . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Moreover , ErbB 2 mediated upregulation of urokinase type plasminogen activator receptor ( uPAR ) is reduced by either the PKCalpha inhibitor Go 6976 or the Src inhibitor PP 2 , and the combination of Go 6976 with PP 2 is superior to either agent alone in suppressing uPAR expression and cell invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Urokinase type plasminogen activator receptor ( uPAR ) is expressed on many different cells , including leukocytes . uPAR has been implicated to play a role in neutrophil migration to sites of inflammation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : The prognostic relevance of urokinase type plasminogen activator ( u PA ) , u PA receptor ( u PAR ) , and plasminogen activator inhibitor 1 ( PAI 1 ) in gastric carcinoma was demonstrated in an independent patient series . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Previous studies have indicated that the urokinase type plasminogen activator receptor ( uPAR ) can functionally interact with integrins thereby modulating integrin activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Decoy molecules based on PNA DNA chimeras and targeting Sp 1 transcription factors inhibit the activity of urokinase type plasminogen activator receptor ( uPAR ) promoter . ^^^ The expression levels of urokinase type plasminogen activator receptor ( uPAR ) are strongly correlated with metastatic potential in human cancer cell lines of melanoma , breast , lung , and colon . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : Immunohistochemistry was performed in paraffin embedded tissue specimens from 149 invasive breast carcinomas to detect the proteins ets 1 , p 53 , topoisomerase IIalpha , matrix metalloproteinase 7 ( MMP 7 ) and urokinase type plasminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This diptheria toxin uPA fusion protein ( DTAT ) has the advantage over other fusion proteins of targeting malignant glioma cells and the endothelial cells of the neovasculature that express the urokinase type plasminogen activator receptor ( uPAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Aspirin upregulates expression of urokinase type plasminogen activator receptor ( uPAR ) gene in human colon cancer cells through AP 1 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The cell adhesion molecule integrin alphaMbeta 2 associates with the urokinase type plasminogen activator receptor ( uPAR ) on monocytes and neutrophils . uPAR also associates with members of the beta 1 and beta 3 integrins , and it modulates the ligand binding function of these integrins . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The expression of LR 11 , a member of the LDL receptor family and an enhancer of cell surface localization of urokinase type plasminogen activator receptor ( uPAR ) , is increased in cultured SMCs by treatment with PDGF BB . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
DAG was measured in normal epidermal cells and in cells transfected with the human u PA receptor ( u PAR ) gene and stimulated with u PA or ATF . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Besides being a potent inhibitor of protein synthesis in cell free assays , ATF SAP was specifically cytotoxic toward cells expressing human uPAR . ^^^ Competition experiments indicated that both the human uPAR and the LDL related receptor protein are involved in mediating the cell killing ability of ATF SAP . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The effect of MAb H 2 was not caused by blocking cellular activation by u PA / u PAR interaction , as the amino terminal fragment ( ATF ) of u PA , which also activates u PAR , prevented tube formation . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To target malignant uPAR expressing cells and to determine whether uPAR can internalize without ligand binding to alpha ( 2 ) MR , we engineered two recombinant toxins , ATF PE 38 and ATF PE38KDEL . ^^^ ATF PE 38 and ATF PE38KDEL were cytotoxic toward malignant uPAR bearing cells , with IC ( 50 ) values as low as 0 . 02 ng / ml ( 0 . 3 pM ) . ^^^ Radiolabeled ATF PE 38 had high affinity for uPAR ( K ( d ) = 0 . 4 8 nM ) on a variety of different malignant cell types and internalized at a rate similar to that of ATF . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
ATF is catalytically inactive , but suppresses the release of viral particles from the HIV 1 infected cell lines via binding to its receptor CD 87 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Since 80 % of synovial cells express urokinase plasminogen activator receptor ( uPAR ) , we investigated the inhibition of plasmin activation in a collagen induced arthritis ( CIA ) mice model , by expressing a uPA / uPAR antagonist molecule ( ATF ) fused to human serum albumin ( HSA ) to extend its serum half life . ^^^ We showed that the genetic coupling did not significantly reduce the ability of the ATF moiety to interact with its receptor uPAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In clustering analysis , both PLAT and PLAU clustered with the functionally related urokinase plasminogen activator surface receptor ( PLAUR ; 1 . 9 fold ) . ^^^ The expression levels of SERPINB 5 , PLAU , PLAUR and MT 1 correlated with the DBC 1 levels , suggesting previously unknown involvement of DBC 1 in the urokinase plasminogen pathway . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To confirm that these proteins are the murine counterpart of the human u PA receptor ( u PAR ) , a peptide was derived from the murine cDNA clone assigned to represent the murine u PAR due to cross hybridization and pronounced sequence similarity with human u PAR cDNA [ Kristensen , P . , Eriksen , J . , Blasi , F . & Dan , K . ( 1991 ) J . ^^^ Binding of mouse u PA to its receptor showed species specificity in ligand blotting analysis , since mouse u PA did not bind to human u PAR and human u PA did not bind to mouse u PAR . ^^^ In four of the cell lines , mouse u PA bound to two mouse u PAR variant proteins , whereas in the other two cell lines studied , there was only one mouse u PA binding protein . ^^^ Receptor bound mouse u PA could be released by phosphatidylinositol specific phospholipase C treatment , indicating that mouse u PAR is attached to the cell surface by glycosylphosphatidylinositol . ^^^ Purification of the two mouse u PAR variant proteins by diisopropylfluorophosphate inactivated mouse u PA Sepharose affinity chromatography yielded two silver stained bands when analysed by SDS / PAGE , corresponding in electrophoretic mobility to those seen by ligand blotting analysis . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
This antibody , which is also the only one to completely inhibit the binding of DFP inactivated [ 125I ] u PA to U 937 cells , is directed against the u PA binding NH 2 terminal domain of u PAR , a well defined fragment formed by limited chymotrypsin digestion of purified u PAR , demonstrating the functional independence of the u PA binding domain as well as the critical role of u PAR in the assembly of the cell surface plasminogen activation system . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Retinal pigment epithelial cell surface u PAR was assayed by measuring the amount of functional urokinase plasminogen activator ( u PA ) bound to cells at saturation . ^^^ Recombinant soluble u PAR competitively inhibited two chain u PA binding to the surface of thrombin treated RPE cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The specific receptor for u PA ( u PAR ) has also been implicated as an essential modulator in this pathway . ^^^ The tissues were homogenized and the supernatants assayed for u PAR immunoreactivity , u PAR antigen concentration , u PAR binding activity and u PA activity . ^^^ The tumor samples also exhibited highly elevated u PA activity and u PAR antigen relative to the corresponding normal tissues . ^^^ Elevated u PA activity appeared to correlate with elevated u PAR antigen in colorectal cancers , but not in the normal tissues . ^^^ The measurement of u PAR and the u PAR related protein , in addition to u PA activity , could have diagnostic or prognostic value in this type of cancer . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Furthermore , the level of mRNA for the u PA receptor ( u PAR ) was increased by these agents 1 . 2 , 1 . 7 , 1 . 8 and 2 . 5 fold , respectively . ^^^ These results indicated that the pericellular fibrinolytic activity induced by u PA / u PAR is modulated by cAMP in osteoblast like cells . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To understand the role of urokinase ( u PA ) and the urokinase receptor ( u PAR ) in malignant astrocytoma cell invasion of normal brain , astrocytic expression of u PAR and u PA mRNAs were analyzed by riboprobe in situ hybridization in astrocytoma and non neoplastic brain biopsies . ^^^ In eight of eight malignant astrocytomas ( glioblastomas ) , u PAR and u PA mRNA expression was demonstrated , whereas in seven non neoplastic brain biopsies , u PAR and u PA mRNAs were not expressed . ^^^ In one of four low grade and all anaplastic astrocytomas u PAR mRNA was expressed , although u PA mRNA was undetectable . ^^^ Consistent with the mRNA detection , u PAR and u PA proteins were expressed by malignant astrocytes in five of five glioblastoma biopsies . ^^^ To study the tumor margin , U 251MG glioblastoma cells were propagated intracerebrally in a severe combined immunodeficient mouse xenograft ( 28 days ) , and u PA mRNA was found to localize predominantly to the leading tumor edge , whereas u PAR mRNA was expressed throughout the tumor . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase ( u PA ) is expressed in stromal cells and only in tumour cells at invasive foci , urokinase receptor ( u PAR ) in tumour cells , plasminogen activator inhibitor type 1 ( PAI 1 ) in the intratumoral extracellular matrix and plasminogen activator inhibitor type 2 ( PAI 2 ) in tumour cells and stromal cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
By cross linking aliquots of cell lysates with the aminoterminal fragment of the A chain of u PA , containing the receptor binding sequence , we have observed a u PAR concentration at focal contacts in both cell lines . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase PA ( u PA ) was expressed focally , by only five non spindle cell melanomas but in all metastases . u PA expression correlated with occurrence of metastasis . u PA receptor ( u PAR ) was present in one third of all the tumours examined . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Laminin degradation by Co 115 cells was completely inhibited by 100 micrograms / ml of polyclonal anti t PA IgG , by the plasmin inhibitors aprotinin ( 100 micrograms / ml ) or epsilon aminocaproic acid ( EACA ; at 0 . 3 M ) , but not by antibodies against u PA or u PAR nor by nonimmune IgG . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator ( u PA ) receptor ( u PAR ) is a glycosyl phosphatidylinositol anchored membrane protein that promotes pericellular proteolysis and cellular migration . ^^^ Western blot analysis confirmed that the u PA receptor that was cleaved by SPE B is u PAR . ^^^ SPE B released u PAR retained the ability to bind u PA , as determined by u PA affinity chromatography . ^^^ We conclude that SPE B may inhibit u PA binding to monocytic cells by at least two mechanisms : ( 1 ) by decreasing the level of functional cell surface u PAR and ( 2 ) by releasing a soluble form of u PAR that competes with the cellular receptor for ligand . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We report here that a yeast derived genetic conjugate between human serum albumin and the 1 135 N terminal residues of urokinase ( u PA ) competitively inhibits the binding of exogenous and endogenous u PA to its cell anchored receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The addition of anti u PA receptor ( u PAR ) monoclonal antibodies to the assays selectively suppressed the mitogenic effect exerted by u PA , but not that of t PA , and the amino terminal fragment of u PA , containing the EGF like domain and the kringle module , did not elicit any mitogenic activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The NH 2 terminal repeat containing the u PA binding site showed 54 % identity to the human and murine NH 2 terminal domain , compared to 64 % identity between human and mouse u PAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
PTH or PGE 2 increased Bmax 1 . 4 fold and enhanced the u PA receptor ( u PAR ) mRNA level 1 . 4 fold or 2 . 4 fold , respectively . ^^^ Thus , pericellular fibrinolytic activity by u PA / u PAR and PAI 1 is modulated by bone resorbing factors . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Binding of urokinase ( u PA ) to u PAR is species specific , since neither murine ( mu PAR ) nor hu PAR binds u PA from the other species . 1 designed and analyzed a series of exchanges between hu PAR and mu PAR in the N terminal first domain to which ligand binding function had been independently mapped . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
These receptors mediate endocytosis and degradation of u PA / PAI 1 complex bound to the glycosyl phosphatidyl inositol anchored urokinase receptor ( u PAR ) on cell surfaces , and participate , in cooperation with other receptors , in hepatic clearance of activator / PAI 1 complexes and uncomplexed t PA from blood plasma . ^^^ The alpha 2MR and gp 330 mediated endocytosis of a ligand ( u PA / PAI 1 complex ) initially bound to another receptor ( u PAR ) is a novel kind of interaction between membrane receptors . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase ( u PA ) and the urokinase receptor ( u PAR ) , are thought to play a critical role in the invasive and metastatic properties of cancer cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Interaction of urokinase type plasminogenactivator ( u PA ) with its cellular receptor ( u PAR ) induces phosphorylation on tyrosine of a 38 kDa protein . ^^^ We demonstrate by immunoprecipitation that u PAR is associated with a 38 kDa protein that is phosphorylated on tyrosine after u PA treatment of cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Functional aspects include the ligand binding process , the consequences of this binding process for the activation cascade system , the cleavage of u PAR by u PA itself , and the internalization of u PA inhibitor complexes . ^^^ Finally , a number of findings are discussed which support the view that u PA / u PAR are important components in degradation processes during cancer invasion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have found that wounding of an endothelial cell monolayer triggers a marked , rapid and sustained increase in expression of a specific high affinity receptor for u PA ( u PAr ) on the surface of migrating cells . ^^^ Migrating cells displayed an increase in the levels of u PA and u PAr mRNAs , and this increase was mediated by endogenous basic fibroblast growth factor ( bFGF ) . ^^^ This suggests that u PA , produced at increased levels by migrating cells , binds to u PAr whose expression is upregulated on the same cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Treatment of HL 60 , K 562 , THP 1 , and U 937 cells with PMA resulted in an induction of urokinase type PA ( u PA ) , the u PA receptor ( u PAR ) , and PAI types 1 and 2 ( PAI 1 and PAI 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Soluble u PA receptor ( u PAR ) or antibodies that inhibited u PA activity prevented the formation of tubular structures by 59 99 % . epsilon ACA and trasylol which inhibit the formation and activity of plasmin reduced the extent of tube formation by 71 95 % . ^^^ TNFalpha or u PA did not induce tubular structures without additional growth factors . bFGF and VEGF 165 enhanced of the u PAR by 72 and 46 % , but TNFalpha itself also increased u PAR in hMVEC by 30 % . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Western blotting studies , using a monoclonal or a polyclonal antibody specific for the u PA cell surface receptor ( u PAR ) , failed to show evidence of u PAR in resting platelets , whereas , u PAR was found at approximately 54 and approximately 48 kD on U 937 monocytes , which served as a positive control . ^^^ It was concluded that platelet membrane contains a specific , high affinity u PA binding protein that is distinct from u PAR . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Although little PA activity was initially present , the majority was of the urokinase type ( u PA ) as determined by neutralization studies using either a polyclonal antibody against u PA or , since u PA functions in the context of its receptor ( u PAR ) , a monoclonal antibody against u PAR . ^^^ To test whether the active , receptor bound u PA from the cell cultures was cleaving scHGF , iodinated scHGF was added to intact cells in the presence of the antibody against u PAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Diisopropylfluorophosphate treated 125I u PA bound specifically to acid treated monolayered endothelial cells with a Kd of 2 . 83 + / 0 . 61 nM , and Bmax of ( 0 . 11 + / 0 . 01 ) 10 10 ( 6 ) sites / cell . u PAR expression was detected in endothelial cells by Northern blot analysis . ^^^ Thus , endothelial cells was shown to express u PAR which binds u PA specifically . ^^^ Although LPS treatment increased u PAR expression in endothelial cells in a dose dependent manner , the expression of u PA and t PA mRNAs was not altered significantly . ^^^ These findings suggest that the established endothelial cell line , TKM 33 , possesses the characteristics of endothelial cells and they express u PAR on their cell surface , which is occupied by intrinsic u PA secreted from the cells , and that treatment of endothelial cells with LPS changes the cell surface characteristics and inhibited the u PAR expression thus promoting the prothrombotic function concomitantly with increased PAI 1 activity . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Using an established cell line , TKM 33 , from human umbilical vein endothelial cells , the pericellular urokinase type PA ( u PA ) activity and expression of u PA receptor ( u PAR ) were investigated . ^^^ Diisopropylfluoro phosphate treated 125I u PA bound specifically to acid treated monolayered endothelial cells with a Kd of 3 . 46 + / 1 . 17 nM , and Bmax of ( 0 . 09 + / 0 . 04 ) 10 10 ( 6 ) sites / cell . mRNA of u PAR was detected by using Northern blot analysis . ^^^ Thus , these endothelial cells express u PAR which bounds u PA specifically . ^^^ These findings suggest that the established endothelial cell line , TKM 33 , possesses the character of endothelial cells and expresses u PAR on their cell surface which is occupied by intrinsic u PA secreted from the cells . ^^^ The pericellular u PA activity and the expression of u PAR were regulated by protein kinase pathway . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In neoplastic cells the degradation of the extracellular matrix proteins is facilitated by excessive expression of u PA , t PA , and u PAR . ^^^ In many forms of carcinoma increased expression of u PAR and u PA is associated with significantly shorter survival . ^^^ Progressively aggressive neoplastic cells evidence high expression of u PA and u PAR activities , variable expression of t PA , and enhanced PAI 1 and PAI 2 activities . ^^^ Neoplastic prostatic tissue also expresses high u PA activity and the more aggressive the cell line , the greater the number of u PAR and the higher the u PA activity . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The receptor ( u PAR ) for urokinase plasminogen activator ( u PA ) is a three domain protein , GPI anchored to the cell surface , which focuses the enzymatic activity of u PA , and allows the cell surface activation of plasminogen . ^^^ Regulation of the activity of u PA is also mediated by u PAR . ^^^ In addition , u PAR occupancy can also directly transduce migratory signals , like chemotaxis , that do not require the protease activity of u PA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The binding of u PA to its specific cell surface receptor , u PAR , is necessary for the activation of u PA system . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase receptor ( u PAR ) , a protein anchored to cell membrane by a glycosyl phosphatidylinositol , plays a central role in cancer cell invasion and metastasis by binding urokinase plasminogen activator ( u PA ) , thereby facilitating plasminogen activation . ^^^ However , the IGR OV 1 Adria cell line contains the u PAR but does not migrate even in the presence of exogenous u PA , although the parental IGR OV 1 cell line migrates normally in the presence of u PA . ^^^ We show that cell migration induced by u PA u PAR complex is always associated with tyrosine kinase activation for the following reasons : ( 1 ) the blockade of the u PAR by a chimeric molecule ( albumin ATF ) inhibits not only the u PA induced cell migration , but also the signalling in IGR OV 1 line ; ( 2 ) the binding of u PA to u PAR on non migrating IGR OV 1 Adria cells was not associated with tyrosine kinase activation ; ( 3 ) the inhibition of tyrosine kinase also blocked cell migration of IGR OV 1 . ^^^ Therefore tyrosine kinase activation seems to be essential for the u PA induced cell locomotion possibly by the formation of a complex u PAR u PA with a protein whose transmembrane domain can ensure cell signalling . ^^^ Thus , IGR OV 1 and IGR OV 1 Adria cell lines represent a good model for the analysis of the mechanism of u PA u PAR induced cell locomotion . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We have analysed the expression of tissue type PA ( t PA ) , urokinase type PA ( u PA ) , and their respective receptors , annexin 2 and u PAR , in normal and neoplastic cultures of pancreatic cells , as well as in pancreatic tissues , and have examined their role in tumor invasiveness in vitro . ^^^ Annexin 2 is also overexpressed in some tumors ( 5 / 13 ) . u PAR is overexpressed in most tumor samples examined ( 14 / 15 ) , while u PA is weakly detected in a low number of cases ( 3 / 14 ) ; both u PAR and u PA are overexpressed in areas of tumor associated pancreatitis . ^^^ These results support the contention that , in the exocrine pancreas , activation of t PA is more specifically associated to neoplastic transformation and to the invasive phenotype , whereas the induction of u PA / u PAR system might be more relevant to inflammatory or non neoplastic events . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Both the xenograft and the patient ' s tumour showed intense staining for mutant p 53 nuclear protein , and high expression of U PA , PAI and u PAR . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Enhanced invasion is associated with increased u PA , UPAR , PAI 1 , MT MMP 1 , MMP 9 and TIMP 1 expression ; with reduced t PA , MMP 1 and MMP 3 expression ; and with the induction of membrane MMP 9 association . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
In this study we examined the relative levels of u PA , tissue type PA ( t PA ) , and u PAR mRNA expression in human HCC by reverse transcription PCR compared with those expressed in peritumoral hepatic tissues . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Antisense transfection of MNNG / HOS gave the following results : ( 1 ) stable incorporation of the construct into the genome of as clones , as detected by Southern blot analysis ; ( 2 ) decreased mRNA level of u PA , as detected by Northern blot analysis ; ( 3 ) approximately 50 % reduced enzyme expression in cell culture medium and cell homogenate ; and ( 4 ) unchanged cellular proliferation activity and u PAR expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The plasminogen activator , urokinase ( u PA ) , interacts with the u PA receptor ( u PAR ) which results in enhanced plasminogen activation on cell surfaces . ^^^ Intradomain interactions also contribute to the interaction of u PA and u PAR . ^^^ Previous studies have shown that human u PA does not bind to the murine u PAR and murine u PA does not recognize human u PAR . ^^^ To further examine the interaction of the human ligand with the u PAR of a different species , we characterized the binding of human 125I single chain u PA ( scu PA ) to hamster cells . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The presence of urokinase Plasminogen Activator ( u PA ) receptors ( u PAR ) on the surface of synovial cells was investigated by radio ligand binding assay and cross linking and by transmission electron microscopy ( TEM ) of a gold u PA complex . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Endothelial cells express fibrinolytic proteins including : urokinase ( u PA ) and tissue type ( t PA ) plasminogen activators , type 1 ( PAI 1 ) and 2 ( PAI 2 ) plasminogen activator inhibitors , and u PA receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator receptors ( u PAR ) were measured by radioligand binding , cell cross linking , immunoassay , and RNAse protection assay . u PA and plasminogen activator inhibitors ( PAIs ) expression and activities were analyzed by zymography , immunoassay , and RNase protection assay . ^^^ Cell migration and proliferation , studied in Boyden chambers and by microscopic counting , were evaluated after the addition of PDGF , b FGF , and blockade with anti u PA , anti u PAR antibodies , and antisense oligodeoxynucleotides ( aODN ) against u PAR mRNA . ^^^ We have shown that HSC produce u PAR , u PA , and PAI 1 . ^^^ PDGF and b FGF up regulate u PA and u PAR , but not PAI 1 , and exogenous addition of u PA stimulates HSC proliferation , chemotaxis , and chemoinvasion . ^^^ Inhibition of u PA / u PAR with antibodies against u PA or u PAR and with u PAR aODN inhibit the proliferative , chemotactic , and chemoinvasive activity of PDGF and b FGF . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : The expression patterns of urokinasase plasminogen activator ( u PA ) , its cell surface receptor ( u PAR ) , and cathepsin B were analyzed by immunohistochemical techniques in 11 cases of parosteal osteosarcoma and in 4 cases of dedifferentiated parosteal osteosarcoma . ^^^ Tumor cells involved in bone production ( ie , those adjacent to tumor produced bone trabeculae ) exhibited equally strong expression of u PA , u PAR , and cathepsin B , regardless of their histologic grade . ^^^ Expression of u PA , u PAR , and cathepsin B was undetectable in the `` normalized ' ' cells embedded in the well developed tumor bone trabeculae . ^^^ CONCLUSION : These data indicate that u PA and its interacting molecules , such as u PAR and cathepsin B , may have some contributory effects on the metastatic potential of tumor cells in dedifferentiated parosteal osteosarcoma . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The antisense transfection resulted in : ( 1 ) stable incorporation of the vector construct into cellular genome , as demonstrated in Southern blot ; ( 2 ) decreased u PA expression in Northern blot ; ( 3 ) 50 % reduced u PA protein expression in both cell homogenate and cell culture medium ; ( 4 ) unchanged cellular proliferation and u PAR ( urokinase plasminogen activator receptor ) expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Increased expression of u PA and u PAR on monocytes by LDL and Lp ( a ) lipoproteins consequences for plasmin generation and monocyte adhesion . ^^^ As urokinase / urokinase receptor ( u PA / u PAR ) is the trigger of a proteolytic cascade responsible for ECM degradation , we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u PAR and u PA . ^^^ Peripheral blood monocytes , isolated from 10 healthy volunteers , were incubated with 10 to 200 microg / ml of native or oxidised ( ox ) atherogenous lipoproteins for 18 h and cell surface expression of u PA and u PAR was analysed by flow cytometry . ^^^ Both LDL and Lp ( a ) induced a dose dependent increase in u PA ( 1 . 6 fold increase with 200 microg / ml of ox LDL ) and u PAR [ 1 . 7 fold increase with 200 microg / ml of ox Lp ( a ) ] . ^^^ There is a great variability of the response among the donors , some of them remaining non responders ( absence of increase of u PA or u PAR ) even at 200 microg / ml of lipoproteins . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Moreover , TKM 33 expressed the u PA receptor ( u PAR ) which plays an important role in the localization of fibrinolytic activity on cell surface . ^^^ In the present study , we investigated the localization of u PA , t PA , PAI 1 and u PAR in TKM 33 by using immunofluorescence staining technique . ^^^ The endothelial cells were strongly stained with anti PAI 1 , anti u PA and anti u PAR IgGs , and slightly with anti t PA IgG . ^^^ The double immunofluorescence staining with mouse anti u PA IgG and rabbit anti u PAR IgG followed by rhodamine conjugated anti mouse IgG and FITC conjugated anti rabbit IgG showed the co localization of u PA and u PAR on the same section of endothelial cells . ^^^ Although u PA antigen also existed in the cytoplasm of endothelial cells , u PAR antigen did not . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The present morphological study was therefore designed to investigate the occurrence and distribution of the tissue and urokinase plasminogen activators ( t PA and u PA ) , the u PA receptor ( u PAR ) and the plasminogen activator inhibitors ( PAI 1 and PAI 2 ) in normal human testis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
BACKGROUND : Urokinase ( u PA ) and the u PA receptor ( u PAR ) influence tumor invasion and metastasis . 1 . 2 . ^^^ The EJ cells ( expressing the highest u PA antigen levels and the u PAR ) invaded Matrigel . ^^^ The T 24 cells , which expressed the u PAR but do not produce u PA , invaded Matrigel only when pretreated with high molecular weight urokinase ( HMW u PA ) . ^^^ Blocking u PA / u PAR attachment with an anti u PAR monoclonal antibody ( Mab 3936 ) inhibited invasion . ^^^ Thus , bladder cancer cell lines require both u PA and the u PAR to invade Matrigel and modulation of u PAR display directly affects their in vitro invasive capacity . 1 . 5 . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Hyaluronic acid inhibits the expression of u PA , PAI 1 , and u PAR in human synovial fibroblasts of osteoarthritis and rheumatoid arthritis . ^^^ The binding assay of u PA and the immunohistochemical analysis of u PA were employed to detect u PA receptor ( u PAR ) . ^^^ CONCLUSION : Pericellular fibrinolytic activity mediated by the u PA / u PAR system and PAI 1 was attenuated by HA in synovial fibroblasts derived from OA and RA . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
ECs also express t PA receptors ( t PAR ) and u PA receptors ( u PAR ) on their cell surfaces , assembling both enzymes to regulate the cellular fibrinolytic activity . ^^^ Heat shock ( 43 degrees C ) increases the expression of u PA , t PA , PAI 1 , and u PAR by which ECs become more fibrinolytic around the cells . ^^^ Furthermore , because ECs possess t PAR and u PAR on their cell surfaces , the binding of t PA and u PA is a critical event , which affords ECs the localized and condensed fibrinolytic potential . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
AIM : To examine the role of u PA and its receptor ( u PAR ) in colonic epithelial cell migration . ^^^ The function of u PA and u PAR was ablated with antisense oligonucleotides to block expression , with synthetic u PA peptides to block interaction , and with aprotinin to block u PA mediated proteolysis . ^^^ RESULTS : Migration was stimulated two to threefold by exogenous u PA , an effect dependent on u PAR binding but independent of u PA mediated mitogenesis and proteolysis . ^^^ Expression of u PA and u PAR was inhibited by 80 % by the appropriate antisense oligonucleotide . ^^^ Basal migration and the motogenic effects of butyrate , epidermal growth factor , and phorbol 12 myristate 13 acetate were suppressed by the u PAR antisense oligonucleotide ( 40 60 % ) but were at best minimally affected following inhibition of u PA expression and binding . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
To determine the role of the fibrinolytic system in regulating the pathologies associated with lung injury , we examined the effect of bleomycin , an agent that induces the development of pulmonary fibrosis , in mice deficient for plasminogen ( Pg ( ) ( / ) ) , urokinase ( u PA ( ) ( / ) ) , urokinase receptor ( u PAR ( ) ( / ) ) , or tissue plasminogen activator ( t PA ( ) ( / ) ) , and in control wild type ( WT ) mice . ^^^ Levels in u PA ( ) ( / ) and u PAR ( ) ( / ) mice were similar to those in WT mice . ^^^ Histological analysis 14 days after lung injury confirmed enhanced interstitial fibrosis in Pg ( ) ( / ) , u PA ( ) ( / ) , and t PA ( ) ( / ) mice relative to WT and u PAR ( ) ( / ) mice . ^^^ Areas of pulmonary hemorrhage were observed in bleomycin treated WT mice and not in Pg ( ) ( / ) , u PA ( ) ( / ) , and u PAR ( ) ( / ) mice or saline controls . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Lymphocytes and macrophages , which infiltrate rupture sites , contribute to plaque degradation by expressing urokinase ( u PA ) bound to cell membrane by urokinase receptor ( u PAR ) and by secreting metalloproteinase MMP 9 . ^^^ We have previously demonstrated that the uptake of oxidised LDL ( ox LDL ) by monocytes induces an increase of u PA and u PAR expression . ^^^ The present study shows that the expression of u PA and u PAR induced by ox LDL on monocyte surface is suppressed by cerivastatin ( a synthetic inhibitor of HMG CoA reductase , Bayer ) from 2 nM . ^^^ Furthermore , higher concentrations of cerivastatin ( 50 100 nM ) reduce the expression of u PA and u PAR on unstimulated monocytes . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The urokinase like plasminogen activator ( u PA ) present in the media conditioned by tumoral prostatic cells acting as a ligand of the cellular membrane receptor ( u PAR ) , has been identified as the specific factor that modulates this proliferative reaction . ^^^ The present study represents an effort to unravel the intracellular pathway by which u PA activates osteoblastic proliferation and to evaluate the role of cellular receptor u PAR in this proliferative phenomenon . ^^^ We also show that SaOS 2 cells increase their proliferative response when cells are plated onto vitronectin , the second natural ligand of u PAR , and that culturing SaOS 2 cells in the presence of u PA represents a stimuli for u PAR expression . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To determine the effect of vitamin E supplementation on urokinase plasminogen activator ( u PA ) receptor ( u PAR ) expression by neutrophils of dairy cows . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Urokinase plasminogen activator receptors ( u PAR ) , u PA and plasminogen activator inhibitor type 1 ( PAI 1 ) were determined by immunoassay and RNase protection assay . ^^^ Cell migration , evaluated either as chemotaxis or as chemoinvasion , was studied in Boyden chambers after addition of TGF beta 1 , and inhibition with anti u PA and anti u PAR antagonists [ antibodies against u PA and u PAR and antisense oligonucleotides ( aODN ) against u PAR mRNA ] . ^^^ TGF beta 1 up regulates the synthesis and expression of PAI 1 , as well as u PAR expression and exposure at the cell membrane , while it does not affect u PA levels . ^^^ TGF beta 1 dependent chemoinvasion of reconstituted basement membrane exploits the cell associated plasminogen activation system , since it is blocked by monoclonal antibodies against u PA and against various u PAR domains , as well as by anti u PAR aODN . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
OBJECTIVE : To investigate the expression and significance of u PA , u PAR and PAI 2 mRNA in giant cell tumor of bone . ^^^ METHODS : The expressions of u PA , u PAR and PAI 2 mRNA in 42 patients with giant cell tumor ( GCT ) of bone was detected with in situ hybridization . ^^^ RESULTS : The expression rates of u PA , u PAR , and PAI 2 mRNA of multinuclear giant cells ( MGC ) were 64 . 3 % , 71 . 4 % and 40 . 5 % . ^^^ The expression rates of u PA mRNA in MGC , u PA and u PAR mRNA in MC of grade 2 and 3 lesions were significantly higher than those of grade 1 and non recurrent lesions ( P < 0 . 05 ) . ^^^ Close positive relation was observed between the expressions of u PA mRNA of both cells , between the expressions of u PAR and PAI 2 mRNA in MGC and also between the expressions of u PA and u PAR mRNA in MC . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
MMP 3 ( stromelysin 1 ) specifically hydrolyzes urokinase ( u PA ) , yielding a 17 kD NH 2 terminal fragment containing the functionally intact receptor ( u PAR ) binding sequence and a 32 kD COOH terminal fragment containing the intact serine proteinase domain . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : Plasma levels of TF and its inhibitor ( TFPI ) , as well as u PA and its receptor ( u PAR ) were measured using ELISA in 76 patients with malignant tumors and 24 patients with benign tumors . ^^^ U PA and u PAR increased significantly in patients with esophageal and gastric cancer . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Changes in urokinase plasminogen activator ( u PA ) and u PA receptor ( u PAR ) expression at the protein and mRNA level in resting neutrophils and in neutrophils activated by phorbol myristate acetate ( PMA ) were examined . ^^^ PMA increased u PAR mRNA levels but this was accompanied by a decrease ( 2 . 5 fold ; P < 0 . 01 ) in free , unoccupied u PA binding sites . ^^^ Thus , PKC plays a role in the modulation of u PA and u PAR by PMA in bovine neutrophils . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
The platelet induced u PA synthesis was inhibited when the endothelial cells were pre treated with phospholipase C to remove the u PA receptor , or when the platelets were incubated with an antibody that blocks the binding of u PA to u PAR . ^^^ Taken together , these data indicate that u PA present on the platelet surface interacts with u PAR on the endothelial cells and induces the u PA synthesis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
They could contribute to the inhibition of both cell proliferation ( down regulation of cyclin D 1 , PCNA , c myc and up regulation p 21 ( Waf 1 ) , p 19 ( INK4d ) , integrin beta 8 ) and cell invasion , either directly ( decrease in u PA , MMP 9 , u PAR , PAI 1 and increase in anti oncogenes Wnt 5a and H cadherin ) or indirectly by stimulating an anti angiogenic gene ( thrombospondin 2 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
A comparable inhibition of the u PA receptor ( u PAR ) mRNA and protein was also evidenced in the antisense transfected cells compared with the control ones . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Finally , since the action of plasminogen activators is facilitated by the presence of specific receptors on cell surfaces , the analysis included also the u PA receptor ( u PAR ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Immunohistochemical and in situ hybridization studies of the expression of the direct activators of MMP 2 , MT 1 MMP and MT 3 MMP , and the indirect activation system tissue plasminogen activator , urokinase ( u PA ) , its receptor ( u PAR ) , and its inhibitor PAI 1 after middle cerebral artery occlusion / reperfusion were undertaken in basal ganglia samples from 26 adolescent male baboons . ^^^ The expressions of all three MMPs , u PA , u PAR , and PA 1 1 , but not tissue plasminogen activator , were increased from 1 hour after middle cerebral artery occlusion in the ischemic core . mRNA transcripts confirmed the increases in latent MMP 2 , u PA , u PAR , and PAI 1 antigen very early after middle cerebral artery occlusion . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Fibrinogen binding potentiates FGF 2 but not VEGF induced expression of u PA , u PAR , and PAI 1 in endothelial cells . ^^^ The pericellular proteolytic balance is important in these responses , and FGF 2 and VEGF up regulate endothelial cell u PA , u PAR and PAI 1 . ^^^ Changes in mRNA levels of u PA , u PAR and PAI 1 were measured by Northern blot . ^^^ FGF 2 increased u PA , u PAR , and PAI 1 mRNA , but there was a significantly greater induction when fibrinogen was added to FGF 2 at all concentrations . ^^^ VEGF also increased endothelial cell expression of u PA , u PAR and PAI 1 , but this effect was not potentiated by fibrinogen . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
METHODS : The plasma levels of tissue factor ( TF ) , thrombin antithrombin complex ( TAT ) , tissue plasminogen activator ( t PA ) , urokinase plasminogen activator ( u PA ) , urokinase plasminogen activator receptor ( u PAR ) and plasmin antiplasmin complex ( PAP ) were measured by ELISA . ^^^ RESULTS : The plasma levels of TF , TAT , u PA , u PAR and PAP were elevated in gastric or intestinal cancer patients ( P < 0 . 05 ) , while u PA , u PAR remarkably increased in patients with local infiltration , lymph node involvement or distal metastasis ( P < 0 . 01 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
We demonstrate that KS cells and MVEC express the u PA receptor ( u PAR ) and release plasminogen activators and plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ Conditioned medium from KS cells induced invasion and proliferation of MVEC through the u PA / u PAR system . ^^^ These activities were inhibited following antagonization of u PA and u PAR , which also reduced constitutive proliferation and invasion of KS cells and MVEC . ^^^ These data indicate that the u PA / u PAR / PAI 1 system is involved in KS induced endothelial cell invasion , proliferation , and differentiation . ^^^ These observations suggest the potential for application of u PA / u PAR system inhibitors for control of AIDS associated KS , that has a high risk of recurrence with highly active antiretroviral therapy failure , and of other KS forms . . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Plasminogen activators u PA and t PA , their inhibitors PAI 1 and PAI 2 , and the u PA receptor ( u PAR , CD 87 ) are often elevated in solid malignant tumour tissues compared to their normal counterparts . ^^^ Proteolytic factors belonging t the plasminogen activator family ( plasmin , u PA , t PA , u PAR , PAI 1 , and PAI 2 ) , which usually are involved in blood clotting and degradation of blood clots , are also present in healthy and diseased tissue of the kidney , lung , liver , gastro intestinal tract , breast , prostate , ovary , and brain . ^^^ In breast cancer patients , an elevated tumour tissue extract antigen content of u PA , PAI 1 , and u PAR is associated with increased tumour aggressiveness and poor prognosis ; in contrary , an elevated content of t PA and PAI 2 indicates a favourable prognosis . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Proliferation was evaluated as cell number increase , and synoviocytes were treated with 0 . 5 microM and 1 microM RAL with and without urokinase plasminogen activator ( u PA ) and anti u PA / anti u PA receptor ( u PAR ) antibodies . ^^^ Fibrinolytic system components ( u PA , u PAR and plasminogen activator inhibitor ( PAI ) 1 ) were assayed by ELISA with cells treated with 0 . 5 microM and 1 microM RAL for 48 h . u PA activity was evaluated by zymography and a direct fibrinolytic assay . ^^^ U PAR / cell and its saturation were studied by radioiodination of u PA and a u PA binding assay . ^^^ The inhibitory effect of RAL was not additive with u PA / u PAR antagonism . ^^^ RA synoviocytes treated with RAL showed , compared to basal , higher levels of PAI 1 ( 10 . 75 + / 0 . 26 versus 5 . 5 + / 0 . 1 microg / 10 ( 6 ) cells , respectively ; p < 0 . 01 ) , lower levels of u PA ( 1 . 04 + / 0 . 05 versus 3 . 1 + / 0 . 4 ng / 10 ( 6 ) cells , respectively ; p < 0 . 001 ) , and lower levels of u PAR ( 11 . 28 + / 0 . 22 versus 23 . 6 + / 0 . 1 ng / 10 ( 6 ) cells , respectively ; p < 0 . 001 ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
Colon cancer progression is associated with the activation of protein kinase C ( PKC ) , the downregulation of functional E cadherin and an increased expression of the serine protease urokinase ( u PA ) and its receptor ( u PAR ) . ^^^ Our results indicate that , prior to inducing a state of competency for plasminogen dependent scattering , PMA triggers an ordered succession of events where upregulation of the activity of u PA precedes proteolysis of u PAR and active degradation of the extracellular matrix ( ECM ) . ^^^
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA
Interacting proteins: P00749 and Q03405 Pubmed SVM Score :0.0
NA