Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phorbol ester promoting agent, 12-O-tetradecanoylphorbol-13-acetate, enhances plasminogen activator production in hamster cell lines that synthesize plasminogen activator immunologically identical with plasminogen activator of normal hamster lung cells. 12-O-Tetradecanoylphorbol-13-acetate exhibits a high degree of specificity in the type of plasminogen activator evoked, which is always of the lung form. No enhancement of plasminogen activator production was detected in hamster cell lines synthesizing plasminogen activator of different antigenic form, although in the presence of 12-O-tetradecanoylphorbol-13-acetate, cells of one such line initiated synthesis of plasminogen activator of the lung form.
 ...
PMID:Specificity of response in hamster cells induced to produce plasminogen activator by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. 8 Nov 5

A procedure was developed for the purification of a plasminogen activator from human uterine tissue. It involves six consecutive steps: (1) extraction of the plasminogen activator from delipidated uterine tissue with 0.3 M potassium acetate buffer, pH 4.2; (2) ammonium sulphate precipitation; (3) zinc chelate-agarose chromatography; (4) n-butyl-agarose chromatography; (5) concanavalin A-agarose chromatography; and (6) gel filtration on Sephadex G-150. The specific activity of the final plasminogen activator preparation was increased by a factor 4500 as compared with the crude extract. The purified plasminogen activator showed a strong tendency to adsorb to surfaces. This could be effectively prevented by Tween-80. The molecular weight of the plasminogen activator was 64 000 as estimated by gel filtration in 1.0 M NaCl and 69 000 as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. The plasminogen activator consisted of two chains (molecular weights 31 000 and 38 000) connected by disulphide bridges. The smallest chain contained the serine residue of the active site as deduced from the incorporation of the tritium label of [3H]diisopropylphosphofluoridate.
 ...
PMID:Purification and partial characterization of plasminogen activator from human uterine tissue. 12 Oct 55

A functionally active human plasmin light (B) chain derivative, stabilized by the streptomyces plasmin inhibitor leupeptin, was isolated from a partially reduced and alkylated enzyme preparation by an affinity chromatography method with a L-lysine-substituted Sepharose column. This light (B) chain derivative was found to be relatively homogeneous by electrophoretic analysis in both an acrylamide gel/dodecyl sulfate system and on cellulose acetate. It possessed approximately 3% of the proteolytic activity (casein substrate) of the original enzyme, and it incorporated 0.09 mol of [3H]diisopropyl phosphorofluoridate per mol of protein. It contained 3.1 +/- 0.3 carboxymethylated cysteines per mol of protein and can be designated as a CmCys5-light (B) chain (CmCys)3. When this isolated light (B) chain derivative was mixed in equal molar amounts with streptokinase, the mixture developed both human and bovine plasminogen activator activities; the bovine activator activity was approximately 66% of the bovine activator activity of the equimolar human plasmin-streptokinase complex. Although this complex now incorporated 0.50 mol of [3H]diisopropyl phosphorofluoridate per mol of protein, its proteolytic activity, on a molar basis, was the same as the proteolytic activity of the isolated light (B) chain derivative. It was shown by electrophoretic analysis in both an acrylamide gel/epsilon-aminocaproic acid system and on cellulose acetate that the light (B) chain derivative and streptokinase forms an equimolar light (B) chain-streptokinase complex, indicating that the binding site for streptokinase is located on the light (B) chain of the enzyme. A functionally active equimolar light (B) chain-streptokinase complex was also isolated from a partially reduced and alkylated equimolar human plasmin-streptokinase complex by the affinity chromatography method. The plasminogen activator activities (human and bovine) of this light (B) chain-streptokinase complex were similar to those of the plasmin-streptokinase complex from which it was derived. Although this complex incorporated 0.70 mol of [3H]diisopropyl phosphorofluoridate per mol of protein, its proteolytic activity, on a molar basis, was only 14% of proteolytic activity of the plasmin-streptokinase complex.
 ...
PMID:Isolation of a human plasmin-derived, functionally active, light (B) chain capable of forming with streptokinase an equimolar light (B) chain-streptokinase complex with plasminogen activator activity. 13 97

Vascular endothelial cells derived from rabbit vena cava and maintained in continuous culture exhibited properties characteristic of the intact endothelium. These cells were used as a model for characterizing the fibrinolytic components specified by the endothelium. Endothelial cells in culture digested radiolabeled fibrinogen. Digestion resulted from the synthesis and secretion of a plasminogen activator. Fibrinolysis was not detected when cells were grown in medium lacking plasminogen, indicating the absence of plasminogen-independent fibrinolytic enzymes. Phorbol-myristate-acetate increased extracellular plasminogen activator activity dramatically. This increase was prevented when actinomycin D or cycloheximide was included in the growth medium, indicating that new gene expression was required for it. Intracellular plasminogen activator could not be detected unless the cell extracts were exposed briefly to mildly acidic conditions. Mixing experiments between acid-treated and untreated extracts suggested that the cells contained a potent, acid-labile inhibitor of fibrinolysis. As little as 10 mug of protein from whole cell extracts inhibited both cell and urokinase-mediated fibrinolysis by more than 70%. Cell fractionation studies localized the inhibitor to the cytosol whereas plasminogen activator activity was restricted to the membrane-rich fraction. This membrane fraction did not require acidification for activity, suggesting that the inhibitor had been removed and that acidification did not activate a plasminogen proactivator. These observations demonstrate that regulation of endothelial fibrinolytic activity is far more complex than had been anticipated and raise several uncertainties in regard to detecting the presence of plasminogen activators in cells and tissues.
 ...
PMID:Synthesis of a fibrinolytic activator and inhibitor by endothelial cells. 14 64

Cultures of Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) produce 50-fold more of the protease plasminogen activator (PA), than do normal chick embryo fibroblasts. Treatment of RSVCEF cultures with the tumor promoter phorbol myristate acetate (PMA) further enhances (8- to 12-fold) the level of PA activity. Increased levels of PA activity in RSVCEF are observed as early as 1 to 2 hr after PMA treatment. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrates that the PA produced by PMA-treated cultures has a molecular weight identical to that of the PA produced by untreated cultures. PA induction by PMA cannot be accomplished in cell-free extracts, but requires protein synthesis in intact cells. Under serum-free conditions, PMA-treated RSVCEF secrete high levels of PA for 4 to 6 days and undergo pronounced morphological alterations. Modified culture conditions and the use of PMA to induce PA has allowed for the accumulation of large amounts of RSVCEF culture fluid and the subsequent purification of the enzyme. The sensitivity of transformed CEF to PMA and the generation of enhanced proteolytic activity in the cellular microenvironment may provide a model system to examine the role of both PA in malignant transformation and PMA in tumor promotion.
 ...
PMID:Synergistic effect of tumor virus transformation and tumor promoter treatment on the production of plasminogen activator by chick embryo fibroblasts. 21 28

This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis.
 ...
PMID:Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester. 21 37

To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures. Although slightly higher than in chick fibroblast cultures, the level of spontaneously synthesized enzyme is low; it reaches a peak shortly after maximum cell fusion has been completed and then declines. Rous sarcoma virus (RSV) transformation of differentiating myotubes was accomplished by infecting myoblasts with a temperature-sensitive mutant, maintaining cultures at the nonpermissive temperature until completion of fusion and shifting to permissive temperatures at selected times thereafter. RSV transformation, phorbol myristate acetate (PMA) and retinoic acid all induced high levels of plasminogen activator production by differentiating myotubes in the absence of DNA synthesis. In comparison with fibroblasts, virus-induced enzyme synthesis by myogenic cultures proceeded more slowly but ultimately reached comparably high levels. Whereas cAMP strongly repressed RSV- and PMA-induced plasminogen activator production by chick fibroblasts, it weakly stimulated enzyme synthesis by myotubes. This suggests that enzyme induction by RSV and PMA is not mediated primarily through effects on cAMP metabolism.
 ...
PMID:Plasminogen activator in chick embryo muscle cells: induction of enzyme by RSV, PMA and retinoic acid. 21 22

To explore the interaction of tumor promoters and sarcoma virus transformation with cellular regulatory mechanisms, we have studied induction of plasminogen activator synthesis by these agents in a background of changing cyclic nucleotide concentrations. We have confirmed the original report of Wigler and Weinstein (Nature, 259: 232, 1976) that phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces high levels of plasminogen activator production by chick embryo fibroblasts. Sarcoma virus transformation sensitizes the fibroblasts by lowering the threshold concentration for response to the action of PMA, and the effects of transformation and PMA on plasminogen activator synthesis are synergistic rather than additive. The plasminogen activators produced in the PMA-, virus-induced, or synergistically stimulated cultures are indistinguishable. Enzyme production in all three conditions is strongly but reversibly inhibited when cyclic nucleotide levels are raised by exposure to cyclic adenosine-3':5'-monophosphate or cholera toxin. A substantial fraction of the morphological effect that accompanies transformation is not affected by concentrations of cyclic nucleotides that suppress plasminogen activator production, and the two phenomena are therefore at least partially independent expressions of transformation in this system.
 ...
PMID:Modulation of plasminogen activator synthesis in chick embryo fibroblasts by cyclic nucleotides and phorobol myristate acetate. 21 31

The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF). Following PMA treatment of serum-free RSVCEF cultures, PA induction is accompanied by distinct morphological changes, including enhanced cell clustering and the formation of dense cellular aggregates. These alterations in the morphology of the PMA-treated transformed cells are inhibited by several protease inhibitors, including leupeptin, NPGB, SBTI, benzamidine and DFP, the specific inhibitor of serine enzymes. A number of protease inhibitors are ineffective in preventing the PMA-induced morphological changes; these include inhibitors of trypsin, chymotrypsin, elastase, thrombin and, most importantly, plasmin. The use of a fluorescent substrate to assay PA directly demonstrated that the pattern of inhibiton of PA activity correlates exactly with the inhibition of morphological changes. The of 3H-DFP to label and characterize serine zymes in the culture fluid from PMA-treated cells further indicated that PA is the serine protease responsible for the morphological changes. Thus PA itself can catalytically alter cellular behavior in culture independent of plasminogen, until not its only known natural substrate.
 ...
PMID:Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator. 22 74

Low concentrations of Vitamin A stimulated plasminogen activator synthesis (PA) in chick embryo fibroblasts (CEF). It caused a dose dependent and reversible increase in PA synthesis in both normal CEF and CEF infected with a temperature sensitive mutant of Rous Sarcoma virus (RSV-Ts68). Both induction and deinduction of PA could be inhibited by Actinomycin D. Vitamin A also accentuated the morphological changes associated with transformation in the Rous Sarcoma virus infected cells. The effects of Vitamin A on PA synthesis were essentially similar to those of the known tumour promoter, phorbol myristate acetate (PMA). Both Vitamin A and PMA were found to act synergistically with sarcoma gene expression as far as PA synthesis was concerned.
 ...
PMID:Effect of vitamin A on plasminogen activator synthesis by chick embryo fibroblasts. 23 60


1 2 3 4 5 6 7 8 9 10 Next >>