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 new set of monoclonal antibodies was generated against the tissue plasminogen activator (t-PA). One of the antibodies, 1:3 C5, was found to be able to distinguish between the one- and two-chain form of t-PA and also exerted significant amidolytic inhibitory activity. Several of the antibodies, as judged from their binding properties in immunosorbent tests, were found to be suitable for immunoaffinity purification purposes, i.e. 1:3 C5, 1:3 G5, and 1:2 B9. Three of the mabs, 1:2 B9, 1:3 G5 and 2:2 B10, were selectively reactive with the A-chain of t-PA, whereas indirect evidences indicated 1:3 C5 to be reactive with a conformational epitope on the B-chain. Three of the antibodies were reactive with porcine t-PA. This new set of antibodies should prove useful for structure-function investigations of t-PA.
 ...
PMID:Characterization of monoclonal antibodies to human tissue-type plasminogen activator: catalytic inhibition and one-two chain discriminatory reactivities. 247 12

Polyclonal and three monoclonal anti-tissue plasminogen activator (a-t-PA) antibodies (1:3 C5, 1:3 G5 and 2:2 B10) were characterized by using enzyme immunoassay (EIA) in which beta-D-galactosidase was coupled to a-t-PA antibody. Monoclonal antibodies called 2:2 B10 and 1:3 G5, specific for both one-chain and two-chain t-PA, strongly bound to one-chain t-PA purified from cultured melanoma cell lines, but 1:3 C5 antibody bound weakly to such t-PA. When polyclonal t-PA antibody was used as the first reaction antibody immobilized on silicone pieces, few determinants were available for monoclonal antibody used in the second reaction due to previous interaction of these determinants in the first reaction. When t-PA levels in the plasma were determined, the presence of EDTA enhanced the sensitivity of t-PA determination by the present EIA technique. Plasma concentrations of t-PA were measured to be higher with 2:2 B10 monoclonal antibody than with polyclonal antibody as the first antibody. Tissue-PA was mainly detected in the endothelial cells, but not in the muscular layer of the inferior mesenteric artery when immunochemical technique was used with polyclonal t-PA antibody.
 ...
PMID:Characterization of various antibodies against tissue plasminogen activator using highly sensitive enzyme immunoassay. 308 76

The aberrant expression of a plasminogen activator (PA) by Moloney virus (MuLV)-transformed mouse lymphocytes and its relation to cell phenotype and tumor growth have been studied. Nine cultured cell lines were established from neoplastic splenic and thymic tissues obtained from B10 congeneic mice inoculated with MuLV and killed when overtly leukemic. Cell surface markers were assayed by microcytotoxicity tests, the concentration of MuLV p30 and group-specific MuLV gp 70 was determined by radioimmunoassays and the expression of PA activity was assessed in a fibrin-agar plate method. PA activity of 24 h serum-free culture supernatant, intact cells or cell lysates (2 X 10(5) cells/ml) was expressed in International Units by reference to a urokinase standard curve. Tumor extension and cell morphology were investigated by histologic and cytomorphologic analysis. In all cases the cell lines were derived from T cells. PA activity is not expressed by normal lymphocytes, but variations in PA expression were observed in the transformed cells. Five out of nine transformed cell lines showed PA activity with a range of 1.3 to 9.9 IU/ml. No PA activity could be detected in the other cell lines. No correlation was found between PA expression and the cell-surface-expressed phenotype, neither was there any correlation between the PA content, the cytopathological features and the degree and type of organ infiltration. This lack of correlation indicates that there is no relation between PA activity and the expression of the transformed phenotype, and that the presence of PA activity seems to be irrelevant to the tumorigenic capacities of the transformed cell lines.
 ...
PMID:Heterogeneity of plasminogen activator expression in various Moloney virus-induced tumor cell lines. Lack of correlation with tumor growth and cell phenotype. 653 48

The B10/B10.A congenic mouse pair serves as a model for identifying specific genes related to morphogenesis and dysmorphogenesis of the embryonic palate and other organs. The present report describes our initial investigation of the Fraser-Juriloff paradigm, which proposes that susceptibility to malformation results from genetically determined differences in normal developmental patterns. Specifically, we evaluated the relationship between Igf2r gene expression, transforming growth factor-beta (TGF-beta) activation, and cdk4 gene expression. By using in situ hybridization, RNase protection assays, indirect immunofluorescence, Western blots, and bioassays, we show 1) the presence of insulin-like growth factor II (IGF-II), IGF-II receptor (IGF-IIR), IGF-IR, TGF-beta, plasminogen, plasminogen activators [urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA)], and Cdk4 in developing palates; 2) on embryonic day 14 (E14), which is a critical day for palatal growth, B10.A embryos have 82% greater IGF-IIR mRNA than B10; 3) on E14, B10.A embryonic palates have a 57% greater level of active TGF-beta2 than B10, although the total TGF-beta2 is nearly identical; and 4) on E14, B10 embryonic palates have a 52% greater level of Cdk4 mRNA than B10.A palates, a measure of cell cycle progression. Because cellular activation of latent TGF-beta appears to require binding to the mannose-6-phosphate (M6P) binding site of the IGF-IIR and is plasmin and plasminogen activator dependent, the positive correlation of IGF-IIR levels and active TGF-beta2 levels seems to be key. Thus, the strain variation of TGF-beta2/IGF-IIR-mediated growth inhibition in late G1 phase would appear to account for the slower growth and development of B10.A palates relative to B10. Elevated corticosteroid (CORT) exposure in E14 B10.A embryos significantly increases TGF-beta levels, 87% of which is TGF-beta2, as well as the levels of active TGF-beta, 64% of which is TGF-beta2. Without exogenous CORT, B10.A embryos do not have clefts; hence, we present an outline of pathogenesis: slower growing B10.A embryos have an up-regulation of IGF-IIR, which serves to sequester IGF-II from the growth-promoting IGF-IR and to bind more CORT-up-regulated, latent TGF-beta2 for subsequent plasmin-dependent activation; higher levels of TGF-beta2 signaling down-regulate Cdk4 and result in greater palatal growth inhibition at a critical stage of palatogenesis and, thus, cleft palate. We present an epigenetic model of information processing related to cell proliferation. The model is a dynamical network that uses continuous logic to learn its rules from changing conditions.
 ...
PMID:Insulin-like growth factor II receptor, transforming growth factor-beta, and Cdk4 expression and the developmental epigenetics of mouse palate morphogenesis and dysmorphogenesis. 943 20