Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization and time-related production of plasminogen activator (PA) by ovarian granulosa cells was studied by measuring the plasmin-mediated lysis of the chromogenic substrate H-D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide diacetate. Granulosa cells from diethylstilbestrol-implanted immature rats produced both a cell-associated and a secreted PA, as indicated by increased hydrolysis of the substrate by the cells or extracellular medium. The formation of cellular PA was induced by FSH and was detectable as early as 2 h during a 72-h culture, with 80% of the maximal activity present by 6 h. In contrast, negligible PA activity was detected in the extracellular medium until 6-20 h of culture, after which time the secreted PA activity continued to rise throughout the 72-h culture period. Control cells also produced both cellular and secreted PA, but in lower amounts than cells stimulated by FSH. The presence of cellular PA was further indicated by a 2-fold rise in PA activity after solubilization of granulosa cells with increasing concentrations of the detergent Triton X-100. However, freshly prepared granulosa cells had no detectable PA activity in the absence or presence of detergent, suggesting that the PA was synthesized during culture. Actinomycin D and cycloheximide suppressed cellular PA production when added during the first hours of granulosa cell culture, but had little effect when added from 44-48 h of culture. In contrast, both actinomycin D and cycloheximide reduced secreted PA activity from 44-48 h. The expression of cellular PA activity was only partially dependent on the presence of fibrin, while the secreted PA fully required fibrin. These results demonstrate gonadotropin-regulated production of both cellular and secreted types of PA by granulosa cells. The cellular form is produced in the first hours of culture when it is sensitive to macromolecule synthesis inhibitors and is partially dependent on fibrin. The extracellular PA is predominantly secreted after the first 24 h of culture and requires fibrin for its activity. The differential activities of the two types of PA may be involved in the control of hormone-induced processes during granulosa cell differentiation.
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PMID:Production of a cell-associated and secreted plasminogen activator by cultured rat granulosa cells. 293 43

Whether single chain urokinase (scuPA) expresses intrinsic enzymatic activity continues to be a subject of controversy. We report that the activity of scuPA is enhanced by a small plasmin substrate, H-D-valyl-L-leucyl-L-lysine-p-nitroanilide diacetate (D-VLK-p), but not by a second plasmin substrate, H-D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide diacetate (*L*YK-p). D-VLK-p had no effect on the activity of a plasmin insensitive scuPA variant (scuPA-glu158) indicating that native scuPA can be cleaved by plasmin even at saturating concentrations of D-VLK-P. In contrast, D-VLK-P inhibited the activity of the native and scuPA-glu158 complexed with soluble urokinase receptor. Further, D-VLK-p stimulated the enzymatic activity of low molecular weight scuPA (amino acids 144-410) suggesting that D-VLK-P interacts with a second, previously undescribed regulatory site in scuPA.
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PMID:Regulation of single chain urokinase by small peptides. 894 49