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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past decade, the existence of cell-surface receptors for components of the plasminogen system, t-PA, u-PA, plasminogen and plasmin, has been demonstrated. Plasminogen receptors have been detected on virtually all cell types tested, and occupancy has also been demonstrated in biological settings. Characteristic features of plasminogen receptors include their relatively low affinity and their extraordinarily high density on many cells. These receptors recognize the lysine binding sites associated with the kringles of plasminogen. Plasminogen receptors include proteins with carboxyl-terminal lysine residues (enolase and annexin II are representatives) and nonproteins, such as gangliosides. Plasminogen binding to cells enhances plasmin activity by augmenting plasminogen activation, increasing the enzymatic activity of plasmin, and protecting plasmin for inactivation by inhibitors. t-PA receptors serve two major functions, clearance and cell-surface localization. The liver is the main organ for t-PA clearance; parenchymal, endothelial and Kupffer cells are all capable of t-PA uptake. Clearance receptors on these cells are heterogeneous and include ones which recognize the carbohydrate side chains of t-PA and ones which take up t-PA: PAI-1 complexes. Receptors which recognize free t-PA also mediate liver clearance, and alpha 2-MR/LRP is a representative of this latter category. Receptors that localize t-PA on cell surfaces serve a profibrinolytic function. Vascular endothelial cells are rich in such receptors, and annexin II is a representative of these t-PA binding sites. Circulating blood cells also bind t-PA, and some of the sites on these cells are shared with plasminogen. Cells of neuronal origin are capable of binding t-PA with high affinity; and amphoterin, a protein involved in neurite outgrowth, may be a neuronal t-PA receptor. Overall, the plasminogen system is one of the most widely distributed and versatile of the cell surface-proteinase systems. By activating bound plasminogen by cell-bound plasminogen activators, the cell harnesses the broad proteolytic activity of plasmin. Cells can then utilize this activity to perform functions such as assisting in cell migration.
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PMID:Receptors for plasminogen and t-PA: an update. 754 65

Plasmin is a potent extracellular protease specialized in the degradation of fibrin (fibrinolysis). Active plasmin is generated by proteolytic activation of the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Alpha-enolase constitutes a receptor for plasminogen on several leukocyte cell types, serving to localize and promote plasminogen activation pericellularly. However, a role for a -enolase-type plasminogen receptor (PlgR) in myogenesis has never been demonstrated. In this study, we show that C2C12 mouse myoblasts express PlgR, being its expression greatly induced during the differentiation process. A monoclonal antibody against PIgR MAb 11G1, with cell surface-generated plasmin inhibitory abilities, was able to fully abrogate C2C12 myoblast fusion and differentiation in vitro. Moreover, both plasmin activity and PlgR expression were significantly induced in regenerating skeletal muscle in vivo, either in experimentally-injured muscle or in the dystrophic muscle of mdx mouse (an animal model of human Duchenne muscular dystrophy, DMD). The mdx muscle presents better regeneration capacities and less fibrosis than the human DMD muscle; therefore, the increase in PlgR/plasmin activity in mdx muscle suggests an important contribution of the fibrinolytic system in mdx regeneration. This study constitutes the first indication of alpha-enolase-type plasminogen receptor as an important component of skeletal myogenesis, by concentrating and enhancing plasmin generation on the cell surface.
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PMID:Plasmin generation dependent on alpha-enolase-type plasminogen receptor is required for myogenesis. 1451 73

Alpha-enolase (SEN) is a strong plasminogen-binding protein on the surface of group A streptococci (GAS). By flow cytometry and immunofluorescence analyses and using human enolase-specific antibody, human pharyngeal cells (Detroit 562) also were found to express enolase on their surface. Detroit 562 cells preferentially bound to Lys-plasminogen and this binding was inhibited in the presence of a lysine analog, epsilon-aminocaproic acid and by carboxypeptidase-B treatment suggesting that the C-terminal lysine residue of the putative pharyngeal cell receptor(s) may play an important role in plasminogen-binding. The increased plasminogen-binding in the presence of free enolase indicated the presence of an enolase/SEN-specific receptor on the pharyngeal cell surface. GAS, when precoated with Lys-plasminogen, adhered to pharyngeal cells significantly more in numbers than when precoated with fibronectin or laminin. Similarly, GAS adhered also significantly more in numbers to pharyngeal cells which were precoated with Lys-plasminogen. GAS adhered similarly in high numbers when incubated with pharyngeal cells in the presence of soluble plasminogen. The de novo pharyngeal cell-bound protease activity, created as a result of activation of bound plasminogen by t-PA, indicated its potential role in pericellular fibrinolytic activity. Further GAS with tPA-activated plasminogen bound on their surface penetrated through Transwell-grown pharyngeal cells in significantly higher numbers. Together, the results presented in this study highlight a novel function of plasminogen in streptococcal adherence to pharyngeal cells and a newly discovered streptococcal ability to pericellularly invade pharyngeal cells as a result of tPA/endogenous plasminogen activator-mediated proteolytic activity.
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PMID:Plasminogen-mediated group A streptococcal adherence to and pericellular invasion of human pharyngeal cells. 1458 Mar 93

We have developed a strategy to identify putative tissue-type plasminogen activator (tPA)receptors present in pancreatic cancer cells by affinity capture with tPA-Sepharose followed by 2-DE and MALDI-MS PMF. Proteins pulled down from either total lysates or raft membrane fractions were characterized and compared with those from a total lysate of an endothelial cell line (HUVEC) to identify pancreas-restricted tPA receptors. A total of 31 proteins were found by this approach, including annexin A2, already described as a tPA receptor in pancreas and endothelial cells, other proteins acting as tPA receptors (i.e., enolase, cytokeratins 8 and 18) in other tissues, and additional proteins not previously identified as candidate tPA receptors. Confirmation of the results was performed for some of these proteins using immunoblotting. These studies are the basis for further functional analyses on the role of these proteins in the biological effects of tPA.
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PMID:A proteomic approach to the identification of new tPA receptors in pancreatic cancer cells. 1654 79

Schistosoma bovis is a ruminant haematic parasite that lives for years in the mesenteric vessels of the host. The aim of this work was to investigate the ability of adult S. bovis worms to interact with plasminogen, a central component in the host fibrinolytic system. Confocal microscopy analysis revealed that plasminogen bound to the tegument surface of the male-but not female-S. bovis worms and that this binding was strongly dependent on lysine residues. It was also observed that a protein extract of the worm tegument (TG) had the capacity to generate plasmin and to enhance the plasmin generation by the tissue-type plasminogen activator. Proteomic analysis of the TG extract identified 10 plasminogen-binding proteins, among which the major ones were enolase, glyceraldehyde-3-phosphate dehydrogenase and actin. This study represents the first report about the binding of plasminogen to Schistosoma sp. proteins.
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PMID:Schistosoma bovis: plasminogen binding in adults and the identification of plasminogen-binding proteins from the worm tegument. 1696 83

Human processed lipoaspirate is a source of multipotent adult stem cells that are able to differentiate between mesenchymal and neurogenic lineage. We characterized PLA cells by cytometry and then they were cultured to induce differentiation into myogenic and neurogenic lineage. Lipoaspirates were digested with collagenase to obtain the pellet, which was labelled with anti-CD44, anti-CD45, and anti-CD90. We used BD FACS Calibur flow cytometer to acquire cellular events. Some cells were cultured at 37 degrees C and 5% CO(2) in neurogenic or myogenic medium and analysed by immunocytochemistry, using Neuron specific enolase, Vimentin, Glial fibrillary acidic protein, Tau, MAP2 to confirm neurogenic differentiation, MyoD1, Myosin heavy chain, Actin smooth muscle, vimentin to confirm myogenic differentiation. The cytometry results suggest that a part of the cells are of a mesenchymal origin, among which there are progenitor endothelial cells and leucocytes. Microscopy observation already reveals neuronal morphology and longitudinal multinucleated cells compared to control cells. Neurogenic cells only express NSE (early neuronal progenitor marker), but not GFAP, Tau, MAP2 (mature neuron and glial markers); myogenic cells are positive for MyoD1 and Myosin heavy chain. This demonstrates that lipoaspirate cells are capable of differentiating in vitro over a short period of time, and could be employed in biological and clinical research, like mesenchymal adult stem cells.
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PMID:Characterization and induction of human pre-adipocytes. 1711 45

Plasminogen binding by bacteria is a virulence factor important for the entry and dissemination of bacteria in the body. A wide variety of bacteria bind plasminogen, including both organisms causing disease and components of the normal oral flora. The purpose of this study was to examine the characteristics of plasminogen binding by six clinical isolates of oral streptococci from both dental plaque and inflammatory lesions. All the strains bound plasminogen with approximately the same affinity, and binding was specific and lysine-dependent as evidenced by its inhibition by epsilon-aminocaproic acid. All of the test strains were capable of activating bound plasminogen to plasmin without the addition of a plasminogen activator, and subsequent analysis revealed the presence of streptokinase in all strains. However, the streptococci exhibited fibrinolytic activity only in the presence of plasminogen and this could be inhibited by the addition of epsilon-aminocaproic acid. SDS-PAGE and 2D gel electrophoresis coupled with plasminogen ligand blotting showed that only a subset of the total proteins (2-15) were involved in the binding of plasminogen. Partial identification of the binding proteins revealed that four glycolytic enzymes, enolase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate mutase, were predominant in binding plasminogen. The binding of plasminogen by bacteria from pus did not differ from that of the strains from supragingival plaque. The findings illustrate how apparently innocuous commensal bacteria are capable of utilizing a mechanism that is generally regarded as being of importance to pathogenicity and suggest an additional role of plasminogen binding.
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PMID:Plasminogen binding by oral streptococci from dental plaque and inflammatory lesions. 1831 38

In this study, we demonstrated that the surface-expressed enolase from diarrheal isolate SSU of Aeromonas hydrophila bound to human plasminogen and facilitated the latter's tissue-type plasminogen activator-mediated activation to plasmin. The bacterial surface-bound plasmin was more resistant to the action of its specific physiological inhibitor, the antiprotease alpha(2)-antiplasmin. We found that immunization of mice with purified recombinant enolase significantly protected the animals against a lethal challenge dose of wild-type (WT) A. hydrophila. Minimal histological changes were noted in organs from mice immunized with enolase and then challenged with WT bacteria compared to severe pathological changes found in the infected and nonimmunized group of animals. This correlated with the smaller bacterial load of WT bacteria in the livers and spleens of enolase-immunized mice than that found in the nonimmunized controls. We also showed that the enolase gene could potentially be important for the viability of A. hydrophila SSU as we could delete the chromosomal copy of the enolase gene only when another copy of the targeted gene was supplied in trans. By site-directed mutagenesis, we altered five lysine residues located at positions 343, 394, 420, 427, and 430 of enolase in A. hydrophila SSU; the mutated forms of enolase were hyperexpressed in Escherichia coli, and the proteins were purified. Our results indicated that lysine residues at positions 420 and 427 of enolase were crucial in plasminogen-binding activity. We also identified a stretch of amino acid residues ((252)FYDAEKKEY(260)) in the A. hydrophila SSU enolase involved in plasminogen binding. To our knowledge, this is the first report of the direct involvement of surface-expressed enolase in the pathogenesis of A. hydrophila SSU infections and of any gram-negative bacteria in general.
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PMID:Surface-expressed enolase contributes to the pathogenesis of clinical isolate SSU of Aeromonas hydrophila. 1927 Jan

Schistosoma bovis is a ruminant parasite able to survive prolonged periods in the vasculature of its host without either being cleared by the host defensive systems or inducing thrombotic or coagulation disturbances. This suggests that the parasite modulates both the immune and haemostatic host responses. Previous studies have shown that host plasminogen binds to the surface of S. bovis adult worms, and that a tegument extract from S. bovis fixes and activates host plasminogen, generating plasmin, which in turn could both inhibit blood clotting and dissolve clots. Enolase has been identified among the tegumental proteins that bind plasminogen. The aim of the present study is to determine the physiological role of the enolase found in the tegument of S. bovis adult worms as regards plasminogen-binding and activation, and to confirm its surface exposure on the parasite. The study included the cloning and sequencing of S. bovis enolase cDNA, collection of the corresponding recombinant protein and evaluation of its plasminogen-binding and activation activity, and an exploration of the expression and localization of native enolase in adult worms and lung schistosomulae. Here we show that S. bovis male adult worms express enolase on their tegumental surface and that this protein binds host plasminogen and increases its activation in the presence of host tissue plasminogen activator (t-PA). This suggests that the surface-associated enolase found here is a physiological receptor of plasminogen that plays a role in the activation of the host fibrinolytic system, most probably to avoid blood clot formation on the worm's surface.
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PMID:Cloning and characterization of a plasminogen-binding surface-associated enolase from Schistosoma bovis. 2060 22

Spontaneous activity is an essential attribute of neuronal networks and plays a critical role in their development and maintenance. Upon blockade of activity with tetrodotoxin (TTX), neurons degenerate slowly and die in a manner resembling neurodegenerative diseases-induced neuronal cell death. The molecular cascade leading to this type of slow cell death is not entirely clear. Primary post-natal cortical neurons were exposed to TTX for up to two weeks, followed by molecular, biochemical and immunefluorescence analysis. The expression of the neuronal marker, neuron specific enolase (NSE), was down-regulated, as expected, but surprisingly, there was a concomitant and striking elevation in expression of tissue-type plasminogen activator (tPA). Immunofluorescence analysis indicated that tPA was highly elevated inside affected neurons. Transfection of an endogenous tPA inhibitor, plasminogen activator inhibitor-1 (PAI-1), protected the TTX-exposed neurons from dying. These results indicate that tPA is a pivotal player in slowly progressing activity deprivation-induced neurodegeneration.
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PMID:Activity deprivation induces neuronal cell death: mediation by tissue-type plasminogen activator. 2199 19


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