| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| GAGs alter target enzyme specificity of PCI in such a way that e . g . urokinase ( uPA ) is the preferred target enzyme in the presence of GAGs while in their absence preferentially tissue kallikrein ( TK ) complexes are formed . ^^^ The effect of the GAG binding adhesive glycoprotein vitronectin ( Vn ) on the GAG stimulated inhibition of uPA by PCI was studied using an amidolytic assay . ^^^ In the presence of heparin , Vn protected uPA from inhibition by PCI in a dose dependent manner with respect to both , Vn and heparin concentration . ^^^ In the absence of GAGs , Vn had no effect on the inhibition of uPA by PCI . ^^^ When equimolar concentrations of radiolabelled uPA and TK were incubated with PCI in the presence of heparin , only complexes of PCI with uPA were detectable . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| In vitro , PCI inhibits activated protein C ( APC ) , thrombin , plasma kallikrein ( KK ) and urokinase ( uPA ) and tissue type plasminogen activator ( tPA ) , and we have shown in vivo inhibition of APC , uPA and KK by PCI . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| The role of PCI for urokinase ( uPA ) inhibition in vivo was investigated . ^^^ We therefore developed an enzyme linked immunosorbent assay ( ELISA ) specific for uPA PCI complexes : Rabbit anti PCI IgG was immobilized on a microtiter plate and following incubation with uPA PCI complex containing samples , bound uPA PCI complexes were quantified with a horseradish peroxidase linked monoclonal antibody ( MoAb ) to uPA . ^^^ Using this assay , time , dose , and heparin dependent complexes were detected when uPA was incubated with normal plasma or purified urinary PCI , whereas no complexes were measurable using PCI immunodepleted plasma . ^^^ In these plasma samples uPA PCI complexes were present in a concentration corresponding to 21 % to 25 % of inactive uPA antigen . ^^^ These data suggest that at high uPA concentrations , such as during uPA therapy , plasma PCI might contribute significantly to uPA inhibition in vivo . . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Since the serine protease inhibitor , protein C inhibitor ( PCI ) , is present in seminal plasma at approximately 3 microM , complexes of PCI with urokinase ( uPA ) and tissue type ( tPA ) plasminogen activator were quantitated using sandwich enzyme linked immunosorbent assays ( ELISA ' s ) . ^^^ Seminal plasma ( N = 10 ) collected in the absence of extrinsic inhibitors had a mean of 25 + / 5 ng / ml uPA : PCI , 76 + / 23 ng / ml tPA : PCI , and 4 + / 2 ng / ml of tPA complexes with plasminogen activator inhibitor 1 ( tPA : PAI 1 ) . 93 % of the uPA and 17 % of the tPA antigen in seminal plasma was in complex with PCI and , when complexation was inhibited by collecting semen into an 1 , 10 phenanthrolinium solution , 33 % of the uPA and 7 % of the tPA was complexed to PCI . ^^^ Urine ( N = 10 ) contained 4 + / 1 ng / ml uPA : PCI . ^^^ In purified system , complexation of uPA and tPA to PCI paralleled the inhibition of the enzymes . ^^^ In vitro studies in blood and seminal plasma showed that heparin stimulated complexation of uPA and tPA with PCI , suggesting that negatively charged glycosaminoglycans in blood vessels and in the reproductive system may regulate PCI reactions with uPA and tPA . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Inhibition of activated protein C ( APC ) , urokinase plasminogen activator ( uPA ) , tissue plasminogen activator ( tPA ) , thrombin , factor Xa ( Xa ) , factor XIa ( XIa ) and plasma kallikrein ( KK ) by PCI was found to be dependent on the size of the polysaccharide . ^^^ Differences in heparin stimulation were more pronounced for thrombin , APC , uPA , tPA and XIa , whereas inactivation of Xa by PCI was less dependent on the presence of heparin , and kallikrein showed higher potentiation with LMWH than with UF heparin . ^^^ They also show that LMWH is less efficient in stimulating the PCI inhibition of APC , uPA and tPA , which could contribute to the antithrombotic effect of these enzymes . . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Plasma uPA is inhibited by the serine protease inhibitor protein C inhibitor ( PCI ) by the insertion of PCI ' s reactive site loop into the active site of the protease . ^^^ To better understand the structural aspects of this inhibition , 15 reactive site mutants of recombinant PCI ( rPCI ) were assayed for differences in uPA inhibition . ^^^ To explain these altered rates of inhibition , a computer derived molecular model of uPA was generated and docked to a model of PCI to simulate complex formation . ^^^ The changes made by mutagenesis were then recreated in the model of uPA PCI . ^^^ In the model , residues at P 3 ' interact with PCI rather than uPA , consistent with P 3 ' variants demonstrating that little variation from wild type activity . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| In the present study , we showed that although the antigenic levels of PCI in two seminal plasma samples from patients with infertility were normal or slightly elevated , their inhibitory activities toward urokinase plasminogen activator ( uPA ) and tissue type plasminogen activator ( tPA ) were absent . ^^^ A time course analysis of PCI uPA complex formation showed that > 80 % of the complex had been formed within 15 min in normal seminal plasma in the presence of heparin , compared with the total complex formed after 150 min incubation , whereas no response to heparin stimulation was observed in the assays with the two patient samples . ^^^ Western blotting also showed that most of the intact PCI molecules , in normal samples , formed complexes with either uPA or tPA but there was no complex formed in one of the two patient samples and very little complex was observed in the other , suggesting that PCI in the two patient samples is inactive . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| In addition to inhibiting the anticoagulant protein C pathway , PCI also inhibits urinary plasminogen activator ( uPA ) , which is a well known mediator of tumor cell invasion . ^^^ Since PCI itself did not affect the proliferation rate of Caki 1 cells or cell expression of uPA in vitro , the effect of uPA , PCI , heat inactivated PCI and plasminogen activator inhibitor ( PAI ) 1 on the invasive potential of cultured RCC cells was evaluated . ^^^ The in vitro invasiveness of Caki 1 cells , which express uPA , was significantly enhanced by the addition of uPA , and it was inhibited by anti uPA antibody , PCI and PAI 1 , but not by heat inactivated PCI . ^^^ In addition , uPA activity was significantly decreased and uPA PCI complex level was significantly increased in the culture medium of PCI expression vector transfected Caki 1 cells as compared to mock transfected Caki 1 cells . ^^^ These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Within the Leydig repertoire , a PCR product was found for plasminogen activators urokinase plasminogen activator ( uPA ) and tissue plasminogen activator ( 8 wk old cells ) , matriptase 2 ( mLTC 1 ) , kallikrein 21 , SERPINA 5 , SERPINB 2 ( primary cultures ) , and serine peptidase inhibitor Kunitz type 2 ( SPINT 2 ) . ^^^ Matriptase 2 , kallikrein 21 , SPINT 2 , and SERPINA 5 were down regulated , whereas uPA and its receptor were up regulated by human chorionic gonadotropin ( hCG ) via cAMP in the mLTC 1 cells . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Evidence for similar expression of protein C inhibitor and the urokinase type plasminogen activator system during mouse testis development . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Surprisingly , the isolated PCI inhibited the amidolytic activity of urokinase ( u PA ) on Glu Gly Arg pNA ( S 2444 ) in a time dependent manner . ^^^ PCI revealed itself as a non competitive inhibitor of u PA . ^^^ Inhibition of amidolytic activity was found to be associated with the formation of an 1 : 1 equimolar complex with a Mr of 110 , 000 as demonstrated by means of polyacrylamide gel electrophoresis and following Western blotting technique using polyclonal antibodies against u PA and PCI . ^^^ |
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| Interacting proteins: P00749 and P05154 |
Pubmed |
SVM Score :0.0 |
| Plasmin formed as a result of scu PA activity then cleaves scu PA to the mature protease , two chain u PA ( tcu PA ) , which is efficiently and irreversibly inhibited by PAI 3 via the standard serpin mechanism , even on u PAR . ^^^ |
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