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

Cellular receptors for plasminogen and tissue plasminogen activator (t-PA) regulate plasminogen activation and cell-associated proteolytic activity. The characteristics of the interactions of both ligands with monocytes and monocytoid cell lines bear certain similarities, including affinity (kd approximately 1 mumol/L) capacity and susceptibility to carboxypeptidase treatment. Therefore, we have undertaken the present study to determine directly whether t-PA and plasminogen share common binding sites on cells. We found that recombinant human single-chain t-PA (rt-PA) could inhibit the binding of 125I-plasminogen to the cells and, conversely, plasminogen could inhibit 125I-rt-PA binding. This relationship was observed with 9 cell types, including both adherent cells and cells in suspension. In addition, under several conditions of cell treatment, plasminogen and t-PA receptor expression was modulated in parallel. Furthermore, molecules that have been implicated as candidate plasminogen receptors, gangliosides, and an alpha-enolase--related molecule, also interacted with t-PA. These results suggest that at least a component of the binding sites for plasminogen is shared with t-PA. Occupancy of these sites by either or both ligand(s) should result in arming the cells with the proteolytic activity of plasmin.
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PMID:Competition between plasminogen and tissue plasminogen activator for cellular binding sites. 840 Feb 93

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

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, although traditionally considered a glycolytic enzyme, constitutes a receptor for plasminogen on several cell types, serving to localize and promote plasminogen activation pericellularly. Localization of plasmin activity on the cell surface plays a critical role in fibrinolysis and in physiopathological processes involving extracellular matrix remodelling. Previous studies have unambiguously demonstrated that uPA-dependent plasmin generation is necessary for myogenesis in vitro and for muscle regeneration in vivo. However, the implication of alpha-enolase plasminogen receptor in myogenesis had never been investigated. This review focuses on the recently reported expression and function of alpha-enolase plasminogen receptor during myogenesis. Skeletal myoblasts express alpha-enolase plasminogen receptor, being its expression greatly induced during the differentiation process in vitro. MAb 11G1, a monoclonal antibody against anti-alpha-enolase plasminogen receptor, that inhibits plasmin generation, was able to fully abrogate myoblast fusion and differentiation. Moreover, both plasmin activity and alpha-enolase plasminogen receptor expression were significantly augmented in injury-induced regenerating muscle of wild type mice and in the dystrophic muscle of mdx mice, an animal model of Duchenne muscular dystrophy (DMD). Altogether, these results indicate that the plasminogen activation (PA) system is an important component of skeletal myogenesis in vitro and in vivo. In particular, the expression of alpha-enolase plasminogen receptor may serve to concentrate and enhance plasmin generation on the cell surface of migratory myoblasts contributing to efficient muscle repair.
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PMID:Alpha-enolase plasminogen receptor in myogenesis. 1557 44

Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cognitive function and early dementia or clinically probable Alzheimer's disease (AD). Oxidative stress plays a significant role in AD and is increased in the superior/middle temporal gyri of MCI subjects. Because AD involves hippocampal-resident memory dysfunction, we determined protein oxidation and identified the oxidized proteins in the hippocampi of MCI subjects. We found that protein oxidation is significantly increased in the hippocampi of MCI subjects when compared to age- and sex-matched controls. By using redox proteomics, we determined the oxidatively modified proteins in MCI hippocampus to be alpha-enolase (ENO1), glutamine synthetase (GLUL), pyruvate kinase M2 (PKM2) and peptidyl-prolyl cis/trans isomerase 1 (PIN1). The interacteome of these proteins revealed that these proteins functionally interact with SRC, hypoxia-inducible factor 1, plasminogen (PLG), MYC, tissue plasminogen activator (PLAT) and BCL2L1. Moreover, the interacteome indicates the functional involvement of energy metabolism, synaptic plasticity and mitogenesis/proliferation. Therefore, oxidative inactivation of ENO1, GLUL and PIN1 may alter these cellular processes and lead to the development of AD from MCI. We conclude that protein oxidation plays a significant role in the development of AD from MCI and that the oxidative inactivation of ENO1, GLUL, PKM2 and PIN1 is involved in the progression of AD from MCI. The current study provides a framework for future studies on the development of AD from MCI relevant to oxidative stress.
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PMID:Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease. 1646 29

Salmonella enteric serovar Typhi Ty2 is a human specific pathogen and an etiological agent for typhoid fever. Most of Salmonella serotypes produce glycogen which has a comparatively minor role in virulence and colonization, but has a more significant role in survival. Enzymes present in glycolytic pathway of bacteria help bacteria to survive by activating other factors inside host. Numerous pathogenic bacteria species intervene with the plasminogen system, and this plasminogen-enolase association may play a critical role in the virulence of S. Typhi by causing direct damage to the host cell extracellular matrix, possibly by enzymic degradation of extracellular matrix proteins or other protein constituents. In this study, molecular modelling of enolase of Salmonella has been accomplished in silico by comparative modelling; we have then analyzed Human alpha enolase which is a homodimer and serves on epithelial cells with our model. Both Structures were docked by D-tartronate semialdehyde phosphate (TSP) and 3-aminoenolpyruvate phosphate (AEP) enolase inhibitors. Our study shows that salmonella enolase and human enolase have different active sites in their structure. This will help in development of new ligands, more suitable for inhibiting bacterial survival inside host as vaccines for typhoid fever are not fully protective. The study also confirmed that enolase Salmonella and Human Plasminogen suggested direct physical interaction between both of them as the activation loop of plasminogen residues showed conformational changes similar to the tissue type plasminogen activator. Various computational biology tools were used for our present study such as Modeller, Molegro Virtual Docker, Grommacs.
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PMID:Molecular modelling, docking and interaction studies of human-plasmogen and salmonella enolase with enolase inhibitors. 2241 38