Genomes and Genes
Summary: A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation.
- Agarkov A, Chauhan S, Lory P, Gilbertson S, Motin V. Substrate specificity and screening of the integral membrane protease Pla. Bioorg Med Chem Lett. 2008;18:427-31 pubmed..Through the use of parallel synthesis and positional scanning, small tripeptides were identified that are viable substrates for the protease. ..
- Luo D, Lin J, Parent M, Mullarky Kanevsky I, Szaba F, Kummer L, et al. Fibrin facilitates both innate and T cell-mediated defense against Yersinia pestis. J Immunol. 2013;190:4149-61 pubmed publisher..The data suggest that T cells combat plague in conjunction with neutrophils, which require help from fibrin to withstand Y. pestis encounters and effectively clear bacteria...
- Chromy B, Choi M, Murphy G, Gonzales A, Corzett C, Chang B, et al. Proteomic characterization of Yersinia pestis virulence. J Bacteriol. 2005;187:8172-80 pubmed..Differentially expressed proteins not previously reported to contribute to virulence are candidates for more detailed mechanistic studies, representing potential new virulence determinants. ..
- Lathem W, Price P, Miller V, Goldman W. A plasminogen-activating protease specifically controls the development of primary pneumonic plague. Science. 2007;315:509-13 pubmed..Inhibition of Pla expression prolonged the survival of animals with the disease, offering a therapeutic option to extend the period during which antibiotics are effective. ..
- Burggraf D, Trinkl A, Dichgans M, Hamann G. Doxycycline inhibits MMPs via modulation of plasminogen activators in focal cerebral ischemia. Neurobiol Dis. 2007;25:506-13 pubmed..Hemoglobin extravasation was also significantly reduced. Our results suggest that doxycycline may have a potential use as an anti-ischemic compound since it provides microvascular protection by inhibiting the plasminogen system. ..
- Soltani A, Soliday C. Effect of ultrasound on enzymatic activity of selected plasminogen activators. Thromb Res. 2007;119:223-8 pubmedUltrasound has been shown to accelerate enzymatic fibrinolysis with adjunctive plasminogen activators. Additionally, ultrasound is known for interaction with biological substances on molecular level in sonodynamic therapy and ..
- Cao M, Buratini J, Lussier J, Carrière P, Price C. Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle. Reproduction. 2006;131:125-37 pubmedExtracellular matrix remodeling occurs during ovarian follicular development, mediated by plasminogen activators (PAs) and PA inhibitors including protease nexin-1 (PN-1)...
- Baruah D, Dash R, Chaudhari M, Kadam S. Plasminogen activators: a comparison. Vascul Pharmacol. 2006;44:1-9 pubmed..Now a days several newer plasminogen activators with different pharmacokinetic and pharmacodynamic properties have been developed to treat thrombotic ..
- Järvinen H, Laakkonen L, Haiko J, Johansson T, Juuti K, Suomalainen M, et al. Human single-chain urokinase is activated by the omptins PgtE of Salmonella enterica and Pla of Yersinia pestis despite mutations of active site residues. Mol Microbiol. 2013;89:507-17 pubmed publisher..Point mutations of active site residues in Pla and PgtE had different effects on the proteolysis of plasminogen and of scuPA, indicating versatility in omptin proteolysis. ..
- Katono T, Kawato T, Tanabe N, Tanaka H, Suzuki N, Kitami S, et al. Effects of nicotine and lipopolysaccharide on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in human osteoblasts. Arch Oral Biol. 2009;54:146-55 pubmed publisher..We examined the effects of nicotine and LPS on the expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and their inhibitors, including tissue inhibitors of metalloproteinases (TIMPs) and PA inhibitor-1 (..
- Chung T, Wang S, Tsai W. Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles. Biomaterials. 2008;29:228-37 pubmedAccelerating thrombolysis using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles by pressure-driven permeation have been demonstrated in vitro and in vivo in animal models...
- Jin T, Bokarewa M, Zhu Y, Tarkowski A. Staphylokinase reduces plasmin formation by endogenous plasminogen activators. Eur J Haematol. 2008;81:8-17 pubmed publisher..Increased levels of circulating plasminogen (Plg) activators such as tissue- or urokinase-type plasminogen activators (tPA or uPA respectively) are the most common causes of hyperfibrinolysis, occasionally causing major ..
- Bahi A, Dreyer J. Overexpression of plasminogen activators in the nucleus accumbens enhances cocaine-, amphetamine- and morphine-induced reward and behavioral sensitization. Genes Brain Behav. 2008;7:244-56 pubmed..Taken together, these data add further evidence for a significant function of extracellular proteases tPA and uPA in addiction and suggest a differential role of plasminogen activators in this context.
- Haiko J, Suomalainen M, Ojala T, Lähteenmäki K, Korhonen T. Invited review: Breaking barriers--attack on innate immune defences by omptin surface proteases of enterobacterial pathogens. Innate Immun. 2009;15:67-80 pubmed publisher..Modification of lipopolysaccharide by in vivo conditions or by bacterial gene loss has an impact on omptin function. Creation of bacterial surface proteolysis is thus a coordinated function involving several surface structures. ..
- Haiko J, Kukkonen M, Ravantti J, Westerlund Wikström B, Korhonen T. The single substitution I259T, conserved in the plasminogen activator Pla of pandemic Yersinia pestis branches, enhances fibrinolytic activity. J Bacteriol. 2009;191:4758-66 pubmed publisher..The results suggest that Microtus Pla represents an ancestral form of Pla that has evolved into a more efficient plasminogen activator in the pandemic Y. pestis lineages. ..
- Suomalainen M, Lobo L, Brandenburg K, Lindner B, Virkola R, Knirel Y, et al. Temperature-induced changes in the lipopolysaccharide of Yersinia pestis affect plasminogen activation by the pla surface protease. Infect Immun. 2010;78:2644-52 pubmed publisher..The temperature-induced changes in LPS are known to help Y. pestis to avoid innate immune responses, and our results strongly suggest that they also potentiate Pla-mediated proteolysis. ..
- van de Langerijt B, Gijtenbeek J, De Reus H, Sweep F, Geurts Moespot A, Hendriks J, et al. CSF levels of growth factors and plasminogen activators in leptomeningeal metastases. Neurology. 2006;67:114-9 pubmed
- Sebbane F, Jarrett C, Gardner D, Long D, Hinnebusch B. Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc Natl Acad Sci U S A. 2006;103:5526-30 pubmed..Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread. ..
- Valls Seron M, Haiko J, de Groot P, Korhonen T, Meijers J. Thrombin-activatable fibrinolysis inhibitor is degraded by Salmonella enterica and Yersinia pestis. J Thromb Haemost. 2010;8:2232-40 pubmed publisher..Thrombin-activatable fibrinolysis inhibitor (TAFI) has anti-fibrinolytic properties as the active enzyme (TAFIa) removes C-terminal lysine residues from fibrin, thereby attenuating accelerated plasmin formation...
- Flemmig M, Melzig M. Serine-proteases as plasminogen activators in terms of fibrinolysis. J Pharm Pharmacol. 2012;64:1025-39 pubmed publisherThis review should give an overview about the natural human plasminogen activators and their various modified variants as well as similar substances isolated from animals, microorganisms and plants...
- Virtanen O, Sirén V, Multanen J, Farkkila M, Leivo I, Vaheri A, et al. Plasminogen activators and their inhibitors in human saliva and salivary gland tissue. Eur J Oral Sci. 2006;114:22-6 pubmedThe purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell-free saliva and to investigate their expression in salivary gland tissue...
- Sirén V, Peltonen J, Vaheri A. Plasminogen activators and their inhibitor gene expression in cutaneous NF1-related neurofibromas. Arch Dermatol Res. 2006;297:421-4 pubmed..We wanted to study plasminogen activators, urokinase (uPA) and tissue type (tPA) and their inhibitor PAI-1, which have not earlier been studied ..
- Haiko J, Laakkonen L, Westerlund Wikström B, Korhonen T. Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla. BMC Evol Biol. 2011;11:43 pubmed publisher..Our results stress the evolvability of bacterial ?-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens. ..
- Eren E, Murphy M, Goguen J, van den Berg B. An active site water network in the plasminogen activator pla from Yersinia pestis. Structure. 2010;18:809-18 pubmed publisher..The Pla structure suggests a model for the interaction with plasminogen substrate and provides a more detailed understanding of the catalytic mechanism of omptin proteases. ..
- Tellgren Roth A, Dittmar K, Massey S, Kemi C, Tellgren Roth C, Savolainen P, et al. Keeping the blood flowing-plasminogen activator genes and feeding behavior in vampire bats. Naturwissenschaften. 2009;96:39-47 pubmed publisher..The evolution of vampire bat plasminogen activators can now be linked phylogenetically to the transition in feeding behavior among vampire bat species from ..
- Chen K, Liu J, Lai S, Hsu L, Lee H. Association of plasminogen activators and matrix metalloproteinase-9 proteolytic cascade with blood-CNS barrier damage of angiostrongyliasis. Int J Exp Pathol. 2006;87:113-9 pubmed..The blood-CNS barrier disruption is mediated by primarily two enzyme systems, the plasminogen activators (PAs) and matrix metalloproteinases (MMPs)...
- Galván E, Lasaro M, Schifferli D. Capsular antigen fraction 1 and Pla modulate the susceptibility of Yersinia pestis to pulmonary antimicrobial peptides such as cathelicidin. Infect Immun. 2008;76:1456-64 pubmed publisher..Taken together, our data indicated that Pla might act as a virulence factor not only by processing plasminogen but also by inactivating CAMPs, particularly when F1 is not expressed. ..
- Ramu P, Lobo L, Kukkonen M, Bjur E, Suomalainen M, Raukola H, et al. Activation of pro-matrix metalloproteinase-9 and degradation of gelatin by the surface protease PgtE of Salmonella enterica serovar Typhimurium. Int J Med Microbiol. 2008;298:263-78 pubmed publisher..Our results indicate that PgtE and Pla have diverged in substrate specificity, and suggest that Salmonella PgtE has evolved to functionally mimic mammalian MMPs...
- Aflalo E, Sod Moriah U, Potashnik G, Har Vardi I. Differences in the implantation rates of rat embryos developed in vivo and in vitro: possible role for plasminogen activators. Fertil Steril. 2004;81 Suppl 1:780-5 pubmedTo assess the participation of urokinase-type (uPA) and tissue-type (tPA) plasminogen activators in embryo development and implantation...
- Lo E, Wang X, Cuzner M. Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases. J Neurosci Res. 2002;69:1-9 pubmed..As the mechanisms of deleterious vs. potentially beneficial PA and MMP actions become better defined, it is hoped that new therapeutic targets will emerge for ameliorating the sequelae of brain injury and inflammation. ..
- Miles L, Hawley S, Baik N, Andronicos N, Castellino F, Parmer R. Plasminogen receptors: the sine qua non of cell surface plasminogen activation. Front Biosci. 2005;10:1754-62 pubmedLocalization of plasminogen and plasminogen activators on cell surfaces promotes plasminogen activation and serves to arm cells with the broad spectrum proteolytic activity of plasmin...
- Netzel Arnett S, Mitola D, Yamada S, Chrysovergis K, Holmbeck K, Birkedal Hansen H, et al. Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity. J Biol Chem. 2002;277:45154-61 pubmed..We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases. ..
- de Groot Besseling R, Ruers T, van Kraats A, Poelen G, Ruiter D, de Waal R, et al. Anti-tumor activity of a combination of plasminogen activator and captopril in a human melanoma xenograft model. Int J Cancer. 2004;112:329-34 pubmed..Angiostatin is generated in vitro in a 2-step process. First, plasminogen is converted to plasmin by plasminogen activators. Next, plasmin excises the angiostatin fragment from plasminogen, a process requiring molecules that are ..
- Sugimoto K, Hofmann L, Razavi M, Kee S, Sze D, Dake M, et al. The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions. J Vasc Surg. 2003;37:512-7 pubmed..Low-dose t-PA combined with subtherapeutic heparin is equally efficacious and safe compared with urokinase. Infusions with t-PA were significantly shorter and less expensive than those with urokinase. ..
- Mali R, Cheng M, Chintala S. Plasminogen activators promote excitotoxicity-induced retinal damage. FASEB J. 2005;19:1280-9 pubmed..non-NMDA-type receptors, into the vitreous humor of CD-1 mice and have investigated the role of plasminogen activators (PAs) [tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA)] in excitotoxicity-..
- Li W, Tanaka K, Chiba Y, Kimura T, Morioka K, Uesaka T, et al. Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs. Am J Physiol Heart Circ Physiol. 2003;284:H23-30 pubmed..We conclude that TMLR induces the expression of MMPs, TIMPs, and urokinase-type PA and that these proteinases play an important role in angiogenesis after TMLR. ..
- Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002;3:932-43 pubmed
- Danø K, Behrendt N, Høyer Hansen G, Johnsen M, Lund L, Ploug M, et al. Plasminogen activation and cancer. Thromb Haemost. 2005;93:676-81 pubmed..Therefore for each type of cancer, a combination of protease inhibitors that is optimised with respect to both maximal therapeutic effect and minimal toxic side effects need to be identified. ..
- Svensson M, Sjöbring U, Luo F, Bessen D. Roles of the plasminogen activator streptokinase and the plasminogen-associated M protein in an experimental model for streptococcal impetigo. Microbiology. 2002;148:3933-45 pubmed..An integrated model for superficial infection at the skin is presented...
- Sato J, Schorey J, Ploplis V, Haalboom E, Krahule L, Castellino F. The fibrinolytic system in dissemination and matrix protein deposition during a mycobacterium infection. Am J Pathol. 2003;163:517-31 pubmed..avium from lungs. Thus, plasmin(ogen) functions in limiting progressive fibrosis in the granuloma during a chronic mycobacterial infection. ..
- Bobik A, Tkachuk V. Metalloproteinases and plasminogen activators in vessel remodeling. Curr Hypertens Rep. 2003;5:466-72 pubmed
- Hou R, Tu W, Lee H, Chen K, Chou H, Lai S. Elevation of plasminogen activators in cerebrospinal fluid of mice with eosinophilic meningitis caused by Angiostrongylus cantonensis. Int J Parasitol. 2004;34:1355-64 pubmed..These results suggest that tissue-type plasminogen activator and urokinase-type plasminogen activator may be play a role in the pathogenesis of eosinophilic meningitis of angiostrongyliasis...
- Tomaso H, Reisinger E, Al Dahouk S, Frangoulidis D, Rakin A, Landt O, et al. Rapid detection of Yersinia pestis with multiplex real-time PCR assays using fluorescent hybridisation probes. FEMS Immunol Med Microbiol. 2003;38:117-26 pubmed..We developed and evaluated a highly specific real-time PCR strategy for the detection of Y. pestis, obtaining results within 3 h including DNA preparation. ..
- Gilabert Estelles J, Castello R, Gilabert J, Ramon L, Espana F, Romeu A, et al. Plasminogen activators and plasminogen activator inhibitors in endometriosis. Front Biosci. 2005;10:1162-76 pubmed..Proteolytic status is determined by the imbalance between plasminogen activators and plasminogen activator inhibitors, which are expressed differently depending on the type of lesion ..
- Merchan J, Chan B, Kale S, Schnipper L, Sukhatme V. In vitro and in vivo induction of antiangiogenic activity by plasminogen activators and captopril. J Natl Cancer Inst. 2003;95:388-99 pubmedMany antiangiogenic molecules are proteolytically cleaved from larger plasma proteins. For example, plasminogen activators cleave plasminogen into plasmin, and plasmin is converted into angiostatin in the presence of sulfhydryl donors...
- Kukkonen M, Korhonen T. The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis. Int J Med Microbiol. 2004;294:7-14 pubmed
- Sadowski T, Steinmeyer J. Differential effects of nonsteroidal antiinflammatory drugs on the IL-1 altered expression of plasminogen activators and plasminogen activator inhibitor-1 by articular chondrocytes. Inflamm Res. 2002;51:427-33 pubmed..Expression of mRNA for the plasminogen activators (uPA and tPA) and their inhibitor (PAI-1) were analyzed by RT-PCR-ELISA...
- Kukkonen M, Suomalainen M, Kyllönen P, Lähteenmäki K, Lång H, Virkola R, et al. Lack of O-antigen is essential for plasminogen activation by Yersinia pestis and Salmonella enterica. Mol Microbiol. 2004;51:215-25 pubmed..Loss of O-antigen facilitates Pla functions and invasiveness of Y. pestis; on the other hand, smooth LPS renders plasminogen activator cryptic in S. enterica. ..
- Sulaiman H, Dawson L, Laurent G, Bellingan G, Herrick S. Role of plasminogen activators in peritoneal adhesion formation. Biochem Soc Trans. 2002;30:126-31 pubmed..It is proposed that the persistence of fibrin due to decreased tPA activity following surgery or chronic inflammation plays a major role in peritoneal adhesion formation. ..
- Roes E, Sweep C, Thomas C, Zusterzeel P, Geurts Moespot A, Peters W, et al. Levels of plasminogen activators and their inhibitors in maternal and umbilical cord plasma in severe preeclampsia. Am J Obstet Gynecol. 2002;187:1019-25 pubmed..The higher plasminogen activator inhibitor type 1 levels and lower urokinase plasminogen activator levels in umbilical cord of these patients are suggestive of decreased fibrinolysis in the fetal circulation. ..
- Longstaff C, Whitton C. A proposed reference method for plasminogen activators that enables calculation of enzyme activities in SI units. J Thromb Haemost. 2004;2:1416-21 pubmedA method has been developed for accurately and precisely measuring the activity of a range of plasminogen activators (PAs) used as thrombolytic agents, including streptokinase, tissue plasminogen activator (tPA) and variants, and ..
- Ward P, Leigh J. Genetic analysis of Streptococcus uberis plasminogen activators. Indian J Med Res. 2004;119 Suppl:136-40 pubmedStreptococci produce a diverse range of secreted plasminogen activators capable of converting mammalian plasminogen to plasmin in a species-specific manner...
- Lähteenmäki K, Edelman S, Korhonen T. Bacterial metastasis: the host plasminogen system in bacterial invasion. Trends Microbiol. 2005;13:79-85 pubmed..system by degrading circulating plasmin inhibitors and by influencing the expression levels of mammalian plasminogen activators and activation inhibitors...
- Zhai P, Wakeham N, Loy J, Zhang X. Functional roles of streptokinase C-terminal flexible peptide in active site formation and substrate recognition in plasminogen activation. Biochemistry. 2003;42:114-20 pubmed..Attempts at using a purified C-tail peptide to rescue the activity loss of the truncation mutants failed, suggesting that the integrity of the SK C-terminal peptide is important for the full function of SK. ..
- Rout U, Diamond M. Role of plasminogen activators during healing after uterine serosal lesioning in the rat. Fertil Steril. 2003;79:138-45 pubmedStudy the expression pattern of tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activators during uterine serosal healing after lesioning in a rat model...
- Rakic J, Maillard C, Jost M, Bajou K, Masson V, Devy L, et al. Role of plasminogen activator-plasmin system in tumor angiogenesis. Cell Mol Life Sci. 2003;60:463-73 pubmed..In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications. ..
- Liberatore G, Samson A, Bladin C, Schleuning W, Medcalf R. Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke. 2003;34:537-43 pubmed..DSPA does not promote kainate- or NMDA-mediated neurotoxicity in vivo. These results provide significant impetus to evaluate DSPA in patients with ischemic stroke. ..