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

A hitherto unknown function of granulocyte colony-stimulating factor (G-CSF) was found using cultured endothelial cells. G-CSF stimulated activity of plasminogen activator (PA) in both extracellular and intracellular milieus of endothelial cells obtained from bovine carotid and aortic artery. This effect was dependent on the concentration of G-CSF added to the culture medium and on the treatment time. The extracellular activity was enhanced approximately 5-fold at a concentration of 5,000 colony-forming unit (CFU)/ml (2.6 nM) and in about a 15-hr treatment period. Analyses by fibrin and reverse fibrin autography revealed that activity of PA was much more increased than that of PA inhibitor in endothelial cells treated with G-CSF.
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PMID:Enhancement of plasminogen activator activity in cultured endothelial cells by granulocyte colony-stimulating factor. 246 58

The secretion of plasminogen activators has been implicated in the controlled extracellular proteolysis that accompanies cell migration and tissue remodeling. We found that the human plasminogen activator urokinase (Uk) (Mr 55,000 form) binds rapidly, specifically, and with high affinity to fresh human blood monocytes and to cells of the monocyte line U937. Upon binding Mr 55,000 Uk was observed to confer high plasminogen activator activity to the cells. Binding of the enzyme did not require a functional catalytic site (located on the B chain of the protein) but did require the noncatalytic A chain of Mr 55,000 Uk, since Mr 33,000 Uk did not bind. These results demonstrate the presence of a membrane receptor for Uk on monocytes and show a hitherto unknown function for the A chain of Uk: binding of secreted enzyme to its receptor results in Uk acting as a membrane protease. This localizes plasminogen activation near the cell surface, an optimal site to facilitate cell migration.
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PMID:A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. 388 Jul 60

PDC-109, a protein of unknown function, is a major component of bovine seminal plasma. Using a computer program designed to detect evolutionary relationships between proteins, I find that the PDC-109 protein is similar to the gelatin-binding domain of bovine fibronectin and part of a kringle domain of human tissue-type plasminogen activator (t-PA). The computer-based comparison of the amino acid sequence of PDC-109 with that of the gelatin-binding domain of fibronectin and part of the second kringle domain of t-PA yields scores that are 15.5 standard deviations and 7.8 standard deviations higher, respectively, than were obtained with a comparison of randomized sequences of these proteins. The probability (p) of getting these scores by chance is less than 10(-50) and 3 X 10(-15), respectively. The similarity between the amino acid sequences of PDC-109 and the gelatin-binding domain in fibronectin and the kringle of t-PA suggests some approaches for identifying the functions of PDC-109. Both t-PA and the gelatin-binding domain of fibronectin have adhesive functions, and the gelatin-binding domain promotes viral transformation of fibroblasts in culture. These functions may be associated with the PDC-109 protein.
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PMID:The PDC-109 protein from bovine seminal plasma is similar to the gelatin-binding domain of bovine fibronectin and a kringle domain of human tissue-type plasminogen activator. 404 Jul 57

The distribution of mRNA coding for the members of the wide-spectrum proteinase scavenging system of the alpha-2-macroglobulin family was examined in the mouse: Alpha-2-macroglobulin (MAM), the murinoglobulins (MUG), the alpha-2-macroglobulin receptor (alpha 2MR) and the receptor associated protein, the heparin binding protein-44 (alpha 2MRAP/HBP-44), a component of unknown function. The results demonstrate that MAM is expressed in the mouse embryo exclusively in the liver and not before day 13 of gestation. MUG mRNA was never detected during embryogenesis. On the other hand, both the alpha 2MR and the alpha 2MRAP/HBP-44 messages were present throughout all embryonal stages examined. The distribution of the alpha 2MR mRNA was widespread in most tissues, with stronger signals observed in developing mouse brain, in whisker follicles and in the perifollicular mesenchyme, in lung, liver, kidney, intestine and placenta. The alpha 2MRAP/HBP-44 mRNA was detected predominantly in brain, lung, liver, kidney and placenta. Interestingly, within each tissue the cellular distribution of the alpha 2MR and alpha 2MRAP/HBP-44 mRNA was quite different with the most remarkable extremes observed in kidney and in placenta. The implication of these observations for receptor expression and function are discussed. Northern analysis of adult tissues extended these observations: major signals for MAM and MUG were seen only in liver, while the expression of the alpha 2MR and the alpha 2MRAP/HBP-44 was widespread with highest levels of the 15-kb alpha 2MR mRNA in liver. Kidney was the most abundant source of alpha 2MRAP/HBP-44 mRNA with the 1.8- and 3.6-kb mRNAs, derived from the same gene by alternative mRNA splicing, present in nearly constant ratios in most tissues, except in testis. The notable absence of expression of MAM in the first half of gestation indicates that during this period the receptor is scavenging for proteinases complexed to MAM derived from the maternal circulation or is being used for endocytosis of the other documented ligands, such as plasminogen activator complexes or apolipoprotein E-containing lipoprotein particles.
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PMID:Distribution of mRNA coding for alpha-2-macroglobulin, the murinoglobulins, the alpha-2-macroglobulin receptor and the alpha-2-macroglobulin receptor associated protein during mouse embryogenesis and in adult tissues. 751 54

A hitherto unknown function of midkine (MK) was found in the regulation of fibrinolytic activity of vascular endothelial cells. Recombinant murine MK enhanced plasminogen activator (PA)/plasmin levels in bovine aortic endothelial cells (BAECs) in a dose- and time-dependent manner. After incubation with 10 ng/ml MK for 18 h, PA and plasmin levels increased 6- and 4-fold, respectively. This effect was attributed to a moderate upregulation of urokinase-type PA expression as well as to a significant down-regulation of PA inhibitor-1 (PAI-1) expression. BAECs constitutively synthesized and secreted MK and its production was enhanced 2-fold with 1 microM retinoic acid or 10 microM retinol. It was found that MK served as a substrate for tissue transglutaminase. In the culture medium, MK existed as a transglutaminase-mediated complex of 36 kDa. Addition of anti-MK antibody to BAEC cultures resulted in a decrease of basal PA activity and an increase of basal PAI-1 levels and attenuated the ability of retinol to enhance PA activity 50% and potentiated the ability to increase PAI-1 levels 4-fold. Furthermore, MK and basic fibroblast growth factor (bFGF) acted more than additively in enhancing PA levels. We conclude that in BAECs MK is a novel autocrine factor sustaining the fibrinolytic property. MK functions as a mediator of retinoid and cooperates with bFGF to enhance fibrinolytic activity of BAECs.
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PMID:Midkine enhances fibrinolytic activity of bovine endothelial cells. 772 90

A hitherto unknown function for transglutaminase (TGase; R-glutaminyl-peptide: amine gamma-glutamyltransferase, EC 2.3.2.13) was found in the conversion of latent transforming growth factor-beta (LTGF-beta) to active TGF-beta by bovine aortic endothelial cells (BAECs). The cell-associated, plasmin-mediated activation of LTGF-beta to TGF-beta induced either by treatment of BAECs with retinoids or by cocultures of BAECs and bovine smooth muscle cells (BSMCs) was blocked by seven different inhibitors of TGase as well as a neutralizing antibody to bovine endothelial cell type II TGase. Control experiments indicated that TGase inhibitors and/or a neutralizing antibody to TGase did not interfere with the direct action of TGF-beta, the release of LTGF-beta from cells, or the activation of LTGF-beta by plasmin or by transient acidification. After treatment with retinoids, BAECs expressed increased levels of TGase coordinate with the generation of TGF-beta, whereas BSMCs and bovine embryonic skin fibroblasts, which did not activate LTGF-beta after treatment with retinoids, did not. Furthermore, both TGase inhibitors and a neutralizing antibody to TGase potentiated the effect of retinol in enhancing plasminogen activator (PA) levels in cultures of BAECs by suppressing the TGF-beta-mediated enhancement of PA inhibitor-1 (PAI-1) expression. These results indicate that type II TGase is a component required for cell surface, plasmin-mediated LTGF-beta activation process and that increased expression of TGase accompanies retinoid-induced activation of LTGF-beta.
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PMID:Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells. 809 47

Organophosphate pesticides are a major source of occupational exposure in the United States. Moreover, malathion has been sprayed over major urban populations in an effort to control mosquitoes carrying West Nile virus. Previous research, reviewed by the U.S. Environmental Protection Agency, on the genotoxicity and carcinogenicity of malathion has been inconclusive, although malathion is a known endocrine disruptor. Here, interindividual variations and commonality of gene expression signatures have been studied in normal human mammary epithelial cells from four women undergoing reduction mammoplasty. The cell strains were obtained from the discarded tissues through the Cooperative Human Tissue Network (sponsors: National Cancer Institute and National Disease Research Interchange). Interindividual variation of gene expression patterns in response to malathion was observed in various clustering patterns for the four cell strains. Further clustering identified three genes with increased expression after treatment in all four cell strains. These genes were two aldo-keto reductases (AKR1C1 and AKR1C2) and an estrogen-responsive gene (EBBP). Decreased expression of six RNA species was seen at various time points in all cell strains analyzed: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1), and a gene of unknown function (GenBank accession no. AI859865). Expression changes in all these genes, detected by DNA microarrays, have been verified by real-time polymerase chain reaction. Differential changes in expression of these genes may yield biomarkers that provide insight into interindividual variation in malathion toxicity.
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PMID:Differential gene expression in normal human mammary epithelial cells treated with malathion monitored by DNA microarrays. 1607 77

Mycoplasma hyopneumoniae is a major, economically damaging respiratory pathogen. Although M. hyopneumoniae cells bind plasminogen, the identification of plasminogen-binding surface proteins and the biological ramifications of acquiring plasminogen requires further investigation. mhp182 encodes a highly expressed 102 kDa protein (P102) that undergoes proteolytic processing to generate surface-located N-terminal 60 kDa (P60) and C-terminal 42 kDa (P42) proteins of unknown function. We show that recombinant P102 (rP102) binds plasminogen at physiologically relevant concentrations (K(D) ~ 76 nM) increasing the susceptibility of plasmin(ogen) to activation by tissue-specific plasminogen activator (tPA). Recombinant proteins constructed to mimic P60 (rP60) and P42 (rP42) also bound plasminogen at physiologically significant levels. M. hyopneumoniae surface-bound plasminogen was activated by tPA and is able to degrade fibrinogen, demonstrating the biological functionality of M. hyopneumoniae-bound plasmin(ogen) upon activation. Plasmin(ogen) was readily detected in porcine ciliated airways and plasmin levels were consistently higher in bronchoalveolar lavage fluid from M. hyopneumoniae-infected animals. Additionally, rP102 and rP42 bind fibronectin with K(D) s of 26 and 33 nM respectively and recombinant P102 proteins promote adherence to porcine kidney epithelial-like cells. The multifunctional binding ability of P102 and activation of M. hyopneumoniae-sequestered plasmin(ogen) by an exogenous activator suggests P102 plays an important role in virulence.
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PMID:Mhp182 (P102) binds fibronectin and contributes to the recruitment of plasmin(ogen) to the Mycoplasma hyopneumoniae cell surface. 2195 86