Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By radioimmunoassays established on human derived antigens, PAPP-A, PP5 and PP14 immunoreactivity was detected in placental extracts and blood of pregnant baboons. None of the serial dilution curves suggested parallelism between respective human and baboon samples. Based on slopes of regressed logit-log transformed binding data, PAPP-A demonstrated the greatest degree of interspecies immunological crossreactivity. PP14 showed the least conservation of antigenic determinants. Physicochemical characterization on heparin, zinc chelate and bovine thrombin affinity matrices could not distinguish human from baboon-derived antigens. As in the human, baboon PAPP-A and PP5 were not detected in blood of male or non-pregnant animals. PP14 was detected in baboon follicular fluid, and only PP5 immunoreactivity was measured in culture media of baboon embryos. Of the three antigens, PAPP-A was detected in pregnant baboons at about 61 days gestation, that is, 4 weeks before PP5 and PP14. With the exception of PP14 which attained peak concentration at 118 days of pregnancy, PAPP-A and PP5 concentrations were greatest at term. In conjunction with physicochemical and immunological criteria, these physiological kinetics clearly support a role for developing a baboon model to serve for further studies into feto-maternal signals, particularly antigens such as PAPP-A and PP5.
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PMID:A baboon model for pregnancy-associated antigens (PAPP-A, PP5, PP14). 169 92

By sensitive and specific radioimmunoassays PAPP-A and PP5 were detected in follicular aspirates obtained from women undergoing ovarian hyperstimulation for oocyte harvest prior to in vitro fertilization and embryo transfer. Follicular and pregnancy-derived PAPP-A were immunologically and physicochemically indistinguishable. Similarly, pregnancy- and nonpregnancy-derived PP5 were immunologically indistinguishable. However, in addition to the 18- and 36-K species, a larger species having a molecular size greater than 140K was found in the follicular fluid. Mean follicular PAPP-A and PP5 concentrations were 727 mIU/L and 1376 mAU/L, respectively, with no significant correlation between follicular PAPP-A, PP5, and steroid concentrations. There was, however, a significant but negative relationship with follicular volume. Preliminary in vitro studies indicated that both proteins were synthesized by granulosa cells in preparation for follicular rupture. Follicular PP5, like antithrombin III, interacted reversibly with heparin and thrombin affinity matrices, suggesting a potential biological role as a follicular anticoagulant, whereas PAPP-A, a specific and potent inhibitor of leukocyte elastase, contributes to the maintenance of proteolytic homeostasis and the protection of spermatozoa and embryo against proteolytic attack originating from the maternal leukocytes.
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PMID:Pregnancy-associated plasma protein-A and placental protein 5 in human ovarian follicular fluid. 240 57

1. The biological activities of the proteinase-activated receptor number 2 (PAR-2)-derived peptides, SLIGRL (PP6) SLIGRL-NH2 (PP6-NH2) and SLIGR-NH2 (PP5-NH2) were measured in mouse and rat gastric longitudinal muscle (LM) tissue and in a rat aortic ring preparation and the actions of the PAR-2-derived peptides were compared with trypsin and with the actions of the thrombin receptor activating peptide, SFLLR-NH2 (TP5-NH2). 2. From a neonatal rat intestinal cDNA library, and from intestinal and kidney-derived cDNA, the coding region of the rat PAR-2 receptor was cloned and sequenced, thereby establishing its close sequence identity with the previously described mouse PAR-2 receptor; and this information, along with a reverse-transcriptase (RT) polymerase chain reaction (PCR) analysis of cDNA derived from gastric and aortic tissue was used to establish the concurrent presence of PAR-2 and thrombin receptor mRNA in both tissues. 3. In the mouse and rat gastric preparations, the PAR-2-derived polypeptides, PP6, PP6-HN2 and PP5-NH2 caused contractile responses that mimicked the contractile actions of low concentrations of trypsin (5 u/ml-1; 10 nM) and that were equivalent to contractions caused by TP5-NH2. 4. The cumulative exposure of the rat LM tissue to PP6-NH2 led to a desensitization of the contractile response to this polypeptide, but not to TP5-NH2 and vice versa, so as to indicate a lack of cross-desensitization between the receptors responsive to the PAR-2 and thrombin receptor-derived peptides. 5. In the rat gastric preparation, the potencies of the PAR-2-activating peptides were lower than the potency of TP5-NH2 (potency order: TP5-NH2 > > PP6-NH2 > or = PP6 > PP5-NH2); PP6 was a partial agonist in this preparation. 6. The contractile actions of PP6 and PP6-NH2 in the rat gastric preparation required the presence of extracellular calcium, were inhibited by nifedipine and were blocked by the cyclo-oxygenase inhibitor, indomethacin and by the tyrosine kinase inhibitor, genistein, but not by the kinase C inhibitor, GF109203X. The contractile responses were not blocked by atropine, chlorpheniramine, phenoxybenzamine, propranolol, ritanserin or tetrodotoxin. 7. In a precontracted rat aortic ring preparation, with an intact endothelium, all of the PAR-2-derived peptides caused a prompt relaxation response that was blocked by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME) but not by D-NAME; in an endothelium-free preparation, which possessed mRNA for both the PAR-2 and thrombin receptors, the PAR-2-activating peptides caused neither a relaxation nor a contraction, in contrast with the contractile action of TP5-NH2. The relaxation response to PP6-NH2 was not blocked by atropine, chlorpheniramine, genistein, indomethacin, propranolol or ritanserin. 8. In the rat aortic preparation, the potencies of PP6, PP6-NH2 and PP5-NH2 were greater than those of the thrombin receptor activating peptide, TP5-NH2 (potency order: PP6-NH2 > or = PP6 > PP5-NH2 > TP5-NH2). 9. In the rat aortic preparation, the relaxant actions of the PAR-2-derived peptides were mimicked by trypsin, at concentrations (0.5-1 u ml-1; 1-2 nM) lower than those that can activate the thrombin receptor. 10. The bioassay data obtained with the PAR-2 peptides and with trypsin, along with the molecular cloning/RT-PCR analysis, point to the presence of functional PAR-2 receptors that can activate distinct responses in the gastric and vascular smooth muscle preparations. These responses were comparable to those resulting from thrombin receptor activation in the same tissues, so as to suggest that the receptor for the PAR-2-activating peptides may play a physiological role as far reaching as the one proposed for the thrombin receptor.
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PMID:Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. 876 73

Human tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein (PP5) and matrix-associated serine protease inhibitor (MSPI), is a 32-kDa extracellular matrix (ECM) protein consisting of three tandomly arranged Kunitz-type domains that inhibits plasmin, trypsin, chymotrypsin, cathepsin G and plasma kallikrein but not urokinase and tissue-type plasminogen activators or thrombin. Earlier studies in our laboratory revealed that the production of TFPI-2 is reduced or absent during the tumor progression of human gliomas. In the present study, we investigated the role of TFPI-2 in the invasiveness of the amelanotic melanoma cell line C-32. We stably transfected C-32 cells with a vector capable of expressing TFPI-2 in a sense orientation (0.7 kb). TFPI-2 protein production was then determined by western blotting and the mRNA level by northern blotting in parental and stably transfected (vector and sense) clones. The levels of TFPI-2 protein and mRNA were significantly higher in the sense clones, but neither was detected in parental and vector control clones. In addition, in vitro Matrigel invasion/migration assays revealed that the invasive behavior of sense clones was inhibited compared with the behavior of parental and vector clones. This is the first study to show that the upregulation of TFPI-2 plays a significant role in reducing the invasive behavior of human amelanotic melanomas.
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PMID:Role of tissue factor pathway inhibitor-2 (TFPI-2) in amelanotic melanoma (C-32) invasion. 1144 60