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

Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition.
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PMID:Extracellular proteolysis in the adult murine brain. 834 6

Streptokinase, an extracellular protein produced by Streptococci, is capable of activating the human fibrinolytic zymogen plasminogen. The rate of amidolytic activity of the plasminogen-streptokinase complex is greatly diminished by micromolar concentrations of ATP and heparin oligosaccharides. In addition, the plasminogen activator activity of the plasminogen-streptokinase complex is also inhibited by these effectors. ATP and heparin oligosaccharides show structural similarity, suggesting that the inhibition is caused by binding of these molecules to a common newly formed binding pocket in streptokinase, which appears after interaction with plasminogen. Addition of the bivalent cations Ca2+ and Mg2+ reverses the inhibition caused by ATP and heparin. In the presence of ATP and bivalent cations, the complex between plasminogen and streptokinase develops an autophosphorylating activity whose target is the sequence LTSRPAHG in the 4.5 kDa streptokinase N-terminal peptide, which is an early autolysis peptide. This streptokinase N-terminal peptide, which is essential for streptokinase activating activity, may serve, once phosphorylated, in mechanisms related to the pathogenicity of Streptococci. These studies suggest a critical role for plasminogen in regulating the activity of the streptokinase molecule.
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PMID:ATP-regulated activity of the plasmin-streptokinase complex: a novel mechanism involving phosphorylation of streptokinase. 854 80

Urokinase-type plasminogen activator (uPA) activation of plasminogen is an important mediator of cell migration in many cell types. In the developing avian heart, uPA has been implicated as a mediator of atrioventricular (AV) cushion cell migration; however, the role of the plasminogen/plasmin system has not been examined. The purpose of this study was to test the hypothesis that uPA conversion of plasminogen to plasmin mediates AV cushion cell migration in vitro. Stage 17/18 chicken atrioventricular tissue lysates converted plasminogen into plasmin through uPA activity but no tissue-type plasminogen activator activity was detected. Zymograms on living cultured AV explants also activated plasminogen producing plasmin that degraded extracellular protein. The migratory capacity of cushion cells was assessed in the presence or absence of various test reagents known to alter the plasminogen/plasmin system. Addition of either human or chicken plasminogen or aprotinin (an inhibitor of plasmin) had no effect on cell migration. However, an anti-catalytic uPA antibody that blocked AV uPA activity, significantly decreased cell migration at all concentrations tested. These results showed that uPA mediated a portion of cushion cell migration in vitro. Although AV segments activated plasminogen and degraded extracellular proteins, uPA's functional role in cushion cell migration did not involve the plasminogen/plasmin system.
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PMID:Urokinase regulates embryonic cardiac cushion cell migration without converting plasminogen. 1052 85

A novel serine protease with fibrinolytic activity named CSP was purified from the culture supernatant of the fungus Cordyceps sinensis, a kind of Chinese herbal medicine. Analysis of the purified enzyme by SDS-PAGE indicated that CSP was a single polypeptide chain with an apparent molecular weight of 31 kDa, and N-terminal sequencing revealed that the first ten amino acid residues of the enzyme were Ala-Leu-Ala-Thr-Gln-His-Gly-Ala-Pro-Trp-. When casein was used as a substrate, the proteolytic activity of CSP reached its maximum at pH 7.0 and 40 degrees C. The effect of chemical agents on the enzyme activity indicated that CSP is a serine protease with a free cysteine residue near the active site. It hydrolysed fibrinogen, fibrin and casein with a high efficiency, while hydrolysing bovine serum albumin (BSA) and human serum albumin (HSA) to a lesser extent. CSP was found to be a plasmin-like protease, but not a plasminogen activator, and it preferentially cleaved the A alpha chain of fibrinogen and the alpha-chain of fibrin. Therefore, the extracellular protein CSP may represent a potential new therapeutic agent for the treatment of thrombosis.
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PMID:A novel extracellular protease with fibrinolytic activity from the culture supernatant of Cordyceps sinensis: purification and characterization. 1766 28

Fibroblasts degrade type I collagen, the major extracellular protein found in mammals, during events ranging from bulk tissue resorption to invasion through the three-dimensional extracellular matrix. Current evidence suggests that type I collagenolysis is mediated by secreted as well as membrane-anchored members of the matrix metalloproteinase (MMP) gene family. However, the roles played by these multiple and possibly redundant, degradative systems during fibroblast-mediated matrix remodeling is undefined. Herein, we use fibroblasts isolated from Mmp13(-/-), Mmp8(-/-), Mmp2(-/-), Mmp9(-/-), Mmp14(-/-) and Mmp16(-/-) mice to define the functional roles for secreted and membrane-anchored collagenases during collagen-resorptive versus collagen-invasive events. In the presence of a functional plasminogen activator-plasminogen axis, secreted collagenases arm cells with a redundant collagenolytic potential that allows fibroblasts harboring single deficiencies for either MMP-13, MMP-8, MMP-2, or MMP-9 to continue to degrade collagen comparably to wild-type fibroblasts. Likewise, Mmp14(-/-) or Mmp16(-/-) fibroblasts retain near-normal collagenolytic activity in the presence of plasminogen via the mobilization of secreted collagenases, but only Mmp14 (MT1-MMP) plays a required role in the collagenolytic processes that support fibroblast invasive activity. Furthermore, by artificially tethering a secreted collagenase to the surface of Mmp14(-/-) fibroblasts, we demonstrate that localized pericellular collagenolytic activity differentiates the collagen-invasive phenotype from bulk collagen degradation. Hence, whereas secreted collagenases arm fibroblasts with potent matrix-resorptive activity, only MT1-MMP confers the focal collagenolytic activity necessary for supporting the tissue-invasive phenotype.
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PMID:Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasion. 1954 30

Streptokinase is an extracellular protein, extracted from certain strains of beta hemolytic streptococcus. It is a non-protease plasminogen activator that activates plasminogen to plasmin, the enzyme that degrades fibrin cloth through its specific lysine binding site; it is used therefore as a drug in thrombolytic therapy. The rate of bacterial growth and streptokinase production was studied in condition of excess glucose addition to culture media and its pH maintenance. The streptokinase product of the bacterial culture was preliminary extracted by salt precipitation and then purified by affinity chromatography on plasminogen substituted sepharose-4B in a condition that the plasminogen active site was protected from streptokinase-induced activation. The purity of streptokinase was confirmed by SDS-PAGE and its biological activity determined in a specific streptokinase assay. The results showed that in the fed-batch culture, the rate of streptokinase production increased over two times as compared with the batch culture while at the same time, shortening the streptokinase purification to a single step increased the yield over 95% at the chromatography stage.
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PMID:Production and purification of streptokinase by protected affinity chromatography. 2340 7