Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P05121 and Q07954 Pubmed SVM Score :1.2490539
Our results show that only 32P PAI 1 in complex with a proteinase binds LRP with high affinity and is efficiently endocytosed by cells , indicating that a high affinity site for LRP is generated on PAI 1 only when in complex with a proteinase . 1.2490539^^^ In addition , PAI 1 in complex with different proteinases is shown to cross compete for LRP binding , demonstrating that the binding site is independent of the proteinase and therefore must reside on the PAI 1 portion of the complex . 1.0845849^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.85743442
To assess the involvement of the heparin binding domain of PAI 1 for the interaction with LRP , we determined the equilibrium dissociation constants for the binding to LRP of a panel of PAI 1 mutants with single and multiple amino acid substitutions of the basic residues that constitute the heparin binding site of PAI 1 ( K 65 , K 69 , R 76 , K 80 and K 88 ) . 0.85743442^^^
Interacting proteins: P05121 and Q07954 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: P05121 and Q07954 Pubmed SVM Score :0.0
Complexes between 125I labeled urokinase type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI 1 ) bound to purified alpha 2 macroglobulin ( alpha 2M ) receptor ( alpha 2MR ) / low density lipoprotein receptor related protein ( LRP ) . ^^^ PAI 1 by alpha 2MR / LRP . . ^^^
Interacting proteins: P05121 and Q07954 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: P05121 and Q07954 Pubmed SVM Score :0.0
Chem . 268 , 13691 13696 ) , ligand blotting was used to localize the binding sites for urokinase type plasminogen activator plasminogen activator inhibitor 1 ( PAI 1 ) complexes and for alpha 1 macroglobulin to a proteolytic fragment of LRP containing the second cluster of complement type cysteine rich repeats . ^^^ It also mediates the cellular uptake of the uncomplexed protease tissue type plasminogen activator ( tPA ) , suggesting that the tPA and PAI 1 binding sites on LRP are in close vicinity and might promote cooperative binding of tPA PAI 1 complexes . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
The low density lipoprotein receptor related protein / alpha 2 macroglobulin receptor ( LRP ) mediates endocytosis of a number of structurally unrelated ligands , including complexes of plasminogen activator inhibitor type 1 ( PAI 1 ) and tissue type plasminogen activator ( t PA ) or urokinase plasminogen activator ( u PA ) , free t PA , single chain urokinase ( pro u PA ) , alpha 2 macroglobulin protease complexes , and lipoprotein lipase . ^^^ PAI 1 to LRP . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
We prove that , at 37 degrees C , the 70 kDa fragment is released into the medium , whereas the 22 kDa fragment remains bound to the cell surface . uPA complexed with its other specific inhibitor , PAI 1 , is cleaved into fragments of identical sizes , but the 70 kDa component is internalized via the alpha 2 macroglobulin receptor . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
In addition , gp 330 acts in concert with LRP in type 2 pneumocytes to mediate clearance of a variety of proteins involved in plasminogen activation , including uPA : PAI 1 complexes PAI 1 and pro uPA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Internalization and degradation was mediated by the low density lipoprotein receptor related protein / alpha 2 macroglobulin receptor ( LRP ) in that these processes were inhibited by an anti LRP antibody , recombinant LRP associated protein , urokinase type plasminogen activator PAI 1 complexes , and lactoferrin . ^^^ PAI 1 internalization via LRP . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Previous work has shown that LRP is responsible for mediating the internalization of urinary type plasminogen activator ( uPA ) complexed to plasminogen activator inhibitor type 1 ( PAI 1 ) ( Nykjaer et al . , 1992 ; Herz et al . , 1992 ) . ^^^ PAI 1 complex for LRP ( Kd = 3 nM ) . ^^^ PAI 1 complexes to purified LRP . ^^^ The binding of 125I pro uPA to LRP is blocked by the 39 kDa receptor associated protein , but not by an amino terminal fragment of uPA , which is known to block binding of uPA to the urokinase receptor . 125I Pro uPA can be internalized and degraded by Hep G 2 cells independent of PAI 1 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
PAI 1 , the internalization of uPA . rPN 1 also required alpha 2 MR , since it could be inhibited by the 39 kDa alpha 2 macroglobulin receptor / low density lipoprotein receptor associated protein , a ligand for the alpha 2 MR . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
PAI 1 complexes involve the receptor LRP . ^^^ We demonstrate that fibroblasts degrade both free t PA ( PAI 1 independent ) and t PA complexed with its specific inhibitor PAI 1 ( PAI 1 dependent ) , whereas genetically altered fibroblasts that do not express LRP neither internalize nor degrade these ligands . ^^^ We propose LRP is the receptor for both PAI 1 independent and PAI 1 dependent t PA ligands . . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
In this study , we demonstrate that receptor mediated binding and endocytosis of the t PA PAI 1 complex are largely mediated by a recently identified low density lipoprotein receptor related protein ( LRP ) . ^^^ PAI 1 binding to LRP . ^^^ PAI 1 and LRP on HepG 2 cells as anti LRP antibody , in addition to anti t PA and anti PAI 1 antibodies , was able to immunoprecipitate the 125I t PA . ^^^ PAI 1 complex with LRP on HepG 2 cells was also observed when the unlabeled t PA . ^^^ PAI 1 complex binding and endocytosis on human hepatoma HepG 2 cells and extend the multifunctional nature of LRP as an endocytosis receptor for several structurally and functionally distinct ligands . . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Both LB 6 clone 19 cells , a mouse cell line transfected with the human uPAR cDNA , and the human U 937 monocytic cell line , express in addition to uPAR also the endocytic alpha 2 macroglobulin receptor / low density lipoprotein receptor related protein ( LRP / alpha 2 MR ) which is required to internalize uPAR bound uPA PAI 1 and uPA PN 1 complexes . ^^^ 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 . ^^^ Immuno electron microscopy confirmed the plasma membrane to intracellular translocation of uPAR , and its dependence on LRP / alpha 2 MR in LB 6 clone 19 cells only after binding to the uPA PAI 1 complex . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
A well known antagonist of the alpha 2 macroglobulin receptor ( alpha 2MR / low density lipoprotein receptor related protein ( LRP ) , GST 39kDa protein ( GST 39kDaP ) efficiently inhibited the binding ( IC 50 0 . 7 nM ) of t PA PAI 1 to rat parenchymal liver cells . ^^^ The interaction of t PA PAI 1 with LRP on rat parenchymal liver cells was not Ca 2 ( + ) dependent and is most probably mediated by a specific determinant on PAI 1 , since an anti PAI 1 monoclonal antibody inhibited the binding of t PA PAI 1 , where as free t PA did not . ^^^ The binding of t PA PAI 1 to rat hepatocytes could not be inhibited by a complex of plasmin and alpha 2 antiplasmin nor by various other ligands of LRP like beta VLDL and lactoferrin . ^^^ LRP on rat parenchymal liver cells is responsible for the uptake and degradation of t PA PAI 1 and may therefore be important for the regulation of the t PA levels in the circulation . . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Low density lipoprotein receptor related proteins 1 ( LRP ) and 2 ( gp330 / megalin ) mediate the endocytosis of thrombin PAI 1 , since antagonists of receptor function such as LRP 1 and LRP 2 antibodies and the 39 kDa receptor associated protein blocked 125I thrombin PAI 1 endocytosis and degradation . ^^^ The LRP mediated clearance of exogenously added 125I thrombin by cultured cells was found to be enhanced 5 fold by inclusion of wild type PAI 1 but by only 2 fold when a mutant form of PAI 1 that is unable to bind VN was included . ^^^ The results highlight a novel mechanism for cellular clearance of thrombin involving native VN promoting the interaction of thrombin and PAI 1 and the subsequent endocytosis of the complex by LRP 1 or LRP 2 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
PAI 1 complexes , RAP , and the anti LRP Fab fragment Fab A 8 . ^^^ PAI 1 complex and Fab A 8 binding to LRP by RAP ( IC 50 congruent with 0 . 3 nM ) , whereas in the reverse experiment , competition of t PA . ^^^ PAI 1 complexes and Fab A 8 for RAP binding to LRP could only be shown at high concentrations of competitors ( > / =1 microM ) . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Because low density lipoprotein receptor related protein ( LRP ) binds apoE , alpha 2M , and PAI 1 , it is of interest to see whether the alpha 2M and PAI 1 concentrations in blood differ between epsilon 4 carriers and non carriers . ^^^ Neither alpha 2M levels nor PAI 1 levels differed between epsilon 4 carriers and non carriers , which suggests that the levels of these two proteins in blood do not reflect the status of LRP in individuals with various apoE genotypes . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
In rat hepatoma cells and in mouse embryonic fibroblasts ( MEF 1 ) the clearance of t PA and of t PA 10 PAI 1 was inhibited more than 95 % by receptor associated protein , an inhibitor of LRP mediated clearance , whereas no t PA or t PA 10 PAI 1 clearance was observed in LRP deficient PEA 13 mouse embryonic fibroblasts . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
At the same stages , a prominent expression of plasminogen activator inhibitor type 1 ( PAI 1 ) by spongiotrophoblasts and giant trophoblasts , as well as of LDL receptor related protein ( LRP ) by spongiotrophoblasts and decidual cells could be detected , suggesting a role in regulating extracellular proteolysis in the area of fetomaternal interface . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
To identify the binding sites for RAP , lactoferrin , and plasminogen activator inhibitor 1 ( PAI 1 ) , a bacterial expression system has been developed to produce soluble LRP fragments spanning residues 783 1399 . ^^^ Binding competition experiments show that RAP , PAI 1 , and lactoferrin each inhibit the binding of the others , suggesting that at this site in LRP , RAP acts as a competitive , rather than an allosteric , inhibitor of PAI 1 and lactoferrin binding . . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Using a series of DNA array membranes , we identified a group of hypoxia induced genes that included plasminogen activator inhibitor 1 ( PAI 1 ) , insulin like growth factor binding protein 3 ( IGFBP 3 ) , endothelin 2 , low density lipoprotein receptor related protein ( LRP ) , BCL 2 interacting killer ( BIK ) , migration inhibitory factor ( MIF ) , matrix metalloproteinase 13 ( MMP 13 ) , fibroblast growth factor 3 ( FGF 3 ) , GADD 45 , and vascular endothelial growth factor ( VEGF ) . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
The low density lipoprotein receptor related protein ( LRP ) is a multiligand clearance receptor that removes free tissue type plasminogen activator ( t PA ) or complexes of t PA with plasminogen activator inhibitor type 1 ( PAI 1 ) from the blood circulation or the pericellular space . ^^^ Co receptors are essential for LRP mediated clearance of several ligands ( e . g . glycosaminoglycans for thrombin / protease nexin and lipoprotein lipase , and the urokinase receptor for urokinase / PAI 1 complexes ) . ^^^ In five cell lines from different organs and species degradation of t PA and t PA / PAI 1 was mediated by LRP ( or LRP like receptors ) . ^^^ No degradation of t PA and t PA / PAI 1 occurred in THP 1 or U 937 human monocyte like cells , despite the presence of functional LRP . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
The aim of this study was to establish whether patients with GHD , like those with CVD , show an increase in fibrinogen ( FBG ) , type 1 plasminogen activator inhibitor ( PAI 1 ) , acute phase response proteins ( APR ) , and soluble adhesion molecules . ^^^ PATIENTS AND DESIGN : Concentrations of PAI 1 antigen ( Ag ) , adhesion molecules sE selectin , sP selectin , and intercellular adhesion molecule 1 ( sICAM 1 ) , FBG and levels of APR orosomucoid ( ORM ) , and ' negative APR ' transferrin ( TRF ) were established in 11 panhypopituitary ( PHP ) patients ( eight men and three women , age median 39 . 0 years , body mass index ( BMI ) 27 . 49 + / 3 . 89 kg / m2 ) before and after 12 month replacement with rhGH . ^^^
Interacting proteins: P05121 and Q07954 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: P05121 and Q07954 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: P05121 and Q07954 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 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Three of the nine genes ( VEGF , PAI 1 , and LRP 1 ) had been reported previously as pVHL targets and are known to be hypoxia inducible . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
One receptor for the ApoE protein is the LRP / alpha 2 macroglobulin receptor , which also binds to and endocytoses tPA and plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ This suggests that the impact of apoE 4 on Alzheimer ' s disease is not the result of altered clearance of tPA or PAI 1 by the LRP receptor . . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Ligands that regulate the interaction of uPA with LRP , such as PAI 1 or the PAI 1 derived peptide ( EEIIMD ) , abolished the vasoactivity of tcuPA in vitro and in vivo . ^^^
Interacting proteins: P05121 and Q07954 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 . ^^^ 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 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Plasminogen activator inhibitor 1 ( PAI 1 ) regulates the proteolytic activity of urokinase type plasminogen activator ( uPA ) and there is increasing evidence for a PAI 1 role in regulating cell migration / invasion by other mechanisms like vitronectin ( VN ) binding and lipoprotein receptor related protein ( LRP ) binding . ^^^ We examined the role of PAI 1 to interact with uPA , VN , and LRP in MDA MB 435 breast cancer and SKOV 3 ovarian cancer cells in a wound induced cell migration assay . ^^^ By different experimental conditions with PAI 1 , expressed either by stable transfection or by adenoviral infection ( wild type PAI 1 and an inactive reactive site P 14 mutant , T333R ) or by addition of recombinant PAI 1 and various mutants ( stable wild type , P 14 T333R , reactive center P 1 R346A , reduced VN binding Q123K , and reduced LRP binding R76E ) , we found that the PAI 1 VN interaction was foremost in suppressing wound induced cell migration . ^^^ By contrast , smooth muscle cell wound induced migration was promoted by exogenously added PAI 1 , but this enhancement was dependent on PAI 1 binding to LRP , not binding to VN . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
The diminished expression of LRP and RAP correlated with increased levels of several known extracellular ligands that LRP usually recycles from the extracellular matrix ( ECM ) environment , including PAI 1 , MMP 9 , and TIMP 1 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
As reported previously for PAI 1 , inhibition of uPA by PAI 2 significantly increased the affinity of the complex for LRP ( K ( D ) of 36 nm for uPA PAI 2 versus 200 nm for uPA ) . ^^^ However , unlike PAI 1 , no interaction was observed between LRP and PAI 2 in either the stressed or the relaxed conformation . ^^^ Furthermore , lack of a direct interaction between PAI 2 and LRP implies that downstream signaling events initiated by PAI 1 may not be activated by PAI 2 . . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Tissue type plasminogen activator ( tPA ) regulates vascular contractility through the low density lipoprotein related receptor ( LRP ) , and this effect is inhibited by plasminogen activator inhibitor type 1 ( PAI 1 ) . ^^^ PAI 1 and the PAI 1 derived hexapeptide EEIIMD abolish the vasocontractile activity of tPA and inhibit the tPA mediated interaction between LRP and alphavbeta 3 . tPA induces calcium mobilization from intracellular stores in vascular smooth muscle cells , and this effect is inhibited by PAI 1 , RGD , and antibodies to both LRP and alphavbeta 3 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
Endocytic receptor LRP together with tPA and PAI 1 coordinates Mac 1 dependent macrophage migration . ^^^ Subsequent neutralization of tPA by its inhibitor PAI 1 enhances binding of the integrin protease inhibitor complex to the endocytic receptor LRP ( lipoprotein receptor related protein ) , triggering a switch from cell adhesion to cell detachment . ^^^ Genetic inactivation of Mac 1 , tPA , PAI 1 or LRP but not the protease uPA abrogates macrophage migration . ^^^ The defective macrophage migration in PAI 1 deficient mice can be restored by wild type but not by a mutant PAI 1 that does not interact with LRP . ^^^ In vitro analysis shows that tPA promotes Mac 1 mediated adhesion , whereas PAI 1 and LRP facilitate its transition to cell retraction . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
LRP is a multifunctional receptor that binds and rapidly internalizes at least seven ligands : apolipoprotein E , activated alpha 2 macroglobulin , tissue and urokinase type plasminogen activators , plasminogen activator inhibitor 1 , lipoprotein lipase , and lactoferrin . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
In addition , embryonic fibroblasts lacking LRP are unable to bind , internalize and degrade methylamine activated alpha 2 macroglobulin and complexes of urokinase with plasminogen activator inhibitor 1 . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
This hypothesis is analogous to the concept proposed by Nykjaer et al in which plasminogen activator inhibitor 1 initially binds to uPA to form a complex that secondarily binds to the alpha 2 macroglobulin receptor , leading to internalization of the complex . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
In addition , the 4G / 5G promoter polymorphism of the gene coding for plasminogen activator inhibitor 1 ( PAI 1 ) , the known ligand of LRP with strong antifibrinolytic potential , was ascertained to investigate its possible association with CAD . ^^^
Interacting proteins: P05121 and Q07954 Pubmed SVM Score :0.0
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