Disease relevance of PLG

• A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes [1].
• Its release from platelets by thrombin may protect the growing thrombus against premature dissolution initiated by plasminogen activators released by the endothelium [2].
• Identification of a pituitary factor responsible for enhancement of plasminogen activator activity in breast tumor cells [3].
• We demonstrate that neuraminidase, the second major protein on the virion surface, binds and sequesters plasminogen, leading to higher local concentrations of this ubiquitous protease precursor and thus to increased cleavage of the HA [4].
• Hyperglycemia increased expression from a transforming growth factor-beta(1) promoter luciferase reporter by 2-fold and increased expression from a (-740 to +44) plasminogen activator inhibitor-1 promoter luciferase reporter gene by nearly 3-fold [5].

High impact information on PLG

• To investigate the possible role of proteases in endothelial cell invasiveness in vitro, bovine microvascular endothelial cells (BMEC) grown on collagen gels were treated with phorbol myristate acetate (PMA), a tumor promoter that markedly increases their production of collagenase and plasminogen activator [6].
• Plasminogen, plasminogen activator, protease inhibitors, and a proteolytic activity are shown to be present in bovine follicular fluid [7].
• Follicular plasminogen and plasminogen activator and the effect of plasmin on ovarian follicle wall [7].
• Control experiments established that only the BCG-PM macrophages released H2O2 after stimulation with phorbol myristate acetate, whereas both BCG-PM and thioglycollate-induced macrophages produced superoxide anion and plasminogen activator [8].
• Autocrine angiotensin system regulation of bovine aortic endothelial cell migration and plasminogen activator involves modulation of proto-oncogene pp60c-src expression [9].

Chemical compound and disease context of PLG

• Effect of Helicobacter pylori lipopolysaccharide (LPS) and LPS derivatives on the production of tissue factor and plasminogen activator inhibitor type 2 by human blood mononuclear cells [10].
• The development of granulomatous pulmonary inflammation in rabbits by aerosol challenge. I. Release of plasminogen activator by alveolar macrophages [11].
• However, because aprotinin is a bovine protein, there is a small, but manageable risk of hypersensitivity reactions.Epsilon aminocaproic acid and tranexamic acid are lysine analogs that reduce bleeding by inhibiting the conversion of plasminogen to plasmin, a serine protease responsible for breaking down fibrinogen to fibrin [12].
• In addition, the toxicity of the drug towards EC, its influence on prostacyclin production and release, and on cell-associated plasminogen activator activity was determined [13].

Biological context of PLG

• A mutagenesis strategy comprising nested deletions and random point substitutions indicated roles for both amino and carboxyl-terminal regions of PauA and identified further essential residues within the alpha domain of the plasminogen activator [14].
• Among these, 10 corresponding to the gene for human plasminogen have been analyzed, and 3 that overlap have been shown to extend from kringle 3 through the 3' noncoding region of the gene [15].
• The longest clone that was found was 581 base pairs in length and coded for the C-terminal 107 amino acids of bovine plasminogen, a 3' noncoding region of 246 nucleotides and a poly(A) tail [15].
• A cDNA library was constructed in pBR322 from bovine liver mRNA that was enriched for plasminogen mRNA by polysome immunoprecipitation [15].
• The amino acid sequence of the single polypeptide chain of bovine plasminogen (786 residues, Mr 88092) was determined [16].

Anatomical context of PLG

• Serum-mediated suppression of cell-associated plasminogen activator activity in cultured endothelial cells [17].
• PA inhibitor incorporated into the extracellular matrix may serve an important role in the regulation of plasminogen activator mediated matrix degradation [18].
• A model of protein Ca fibrinolytic activity has a minimum of two components: a secondary messenger formed by protein Ca action on blood cells and plasma, and the subsequent appearance of plasminogen activator in the animal in response to that messenger [19].
• Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity [20].
• We conclude that HSPGs of human bone marrow serve as a reservoir for bFGF, from which it can be released in a biologically active form via a dual mechanism; one involving a putative endogenous phospholipase, the other involving the proteolytic cascade of plasminogen activation [21].

Associations of PLG with chemical compounds

• Digestion with elastase gave three major fragments: kringles (1 + 2 + 3) and kringle 4, both with intact lysine binding sites, and mini-plasminogen [16].
• In porcine plasminogen the sialic acid is mainly NeuAc; the Man alpha 1----6 branch, however, is only partially sialylated [22].
• In the N-glycan of human plasminogen the two antennae are sialylated with N-acetylneuraminic acid (NeuAc), whereas in the bovine counterpart both branches carry significant amounts of N-glycolylneuraminic acid (NeuGc) [22].
• The results show that the N-terminal prolyl residue of PLG is not an essential requirement for this tripeptide's ability to modulate dopamine receptors [23].
• However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal "C5" conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor [24].

Physical interactions of PLG

• Binding of angiogenin to its cell-surface binding protein (actin) followed by dissociation of the angiogenin-actin complex from the cell surface and subsequent activation of tissue-type plasminogen activator/plasmin are likely steps involved in the processes of endothelial cell invasion and angiogenesis [25].

Regulatory relationships of PLG

• SPARC induces the expression of type 1 plasminogen activator inhibitor in cultured bovine aortic endothelial cells [26].
• Inclusion of either inhibitors of PA or of plasmin or antibody against PA in the culture medium as well as depletion of plasminogen from the serum blocked the formation of TGF-beta, suggesting that PA, plasminogen, and the resulting plasmin are essential for activation of LTGF-beta in retinoid-stimulated cells [27].
• The mitogenic signaling pathway but not the plasminogen activator-inducing pathway of basic fibroblast growth factor is mediated through protein kinase C in fetal bovine aortic endothelial cells [28].
• Furthermore, transcytosis of S. aureus M60 across a mammary epithelial cell monolayer was significantly enhanced by the addition of bovine plasminogen and inhibited by aprotinin [29].
• Angiogenin enhances actin acceleration of plasminogen activation [30].

Other interactions of PLG

• Beta-analogs of PLG (L-prolyl-L-leucyl-glycinamide): ex-chiral pool syntheses and dopamine D2 receptor modulating effects [31].
• In addition to its role in lysosome biogenesis, the CI-MPR interacts with a number of different extracellular ligands at the cell surface, including latent transforming growth factor-beta, insulin-like growth factor-II, plasminogen, and urokinase-type plasminogen activator receptor (uPAR), to regulate cell growth and motility [32].
• Transfected BAECs exhibit increased responsiveness to TGF beta 2 by several different criteria including an increase in plasminogen activator inhibitor-1 protein and inhibition of migration and proliferation [33].
• FGF2-mediated upregulation of urokinase-type plasminogen activator expression requires a MAP-kinase dependent activation of poly(ADP-ribose) polymerase [34].
• The three domains, which exhibit similar topology to each other and to the 46 kDa cation-dependent mannose 6-phosphate receptor, assemble into a compact structure with the uPAR/plasminogen and the carbohydrate-binding sites situated on opposite faces of the molecule [32].

Analytical, diagnostic and therapeutic context of PLG

• In contrast, PLG microspheres revealed a burst release without any erosion [35].
• Measuring the heterogeneity of protein loading in PLG microspheres using flow cytometry [36].
• The removal of these low molecular weight substances by ultrafiltration led to a narrower molecular weight distribution compared to the untreated PLG [37].
• A protein that stimulates the production of plasminogen activator and latent collagenase in cultured bovine capillary endothelial cells has been purified 10(6)-fold from term human placenta by using a combination of heparin affinity chromatography, ion-exchange chromatography, and gel chromatography [38].
• This result was further supported by recovery of intact 125I-labeled plasminogen from rabbit milk after its intravenous injection [39].

References