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)

Two different plasma membrane enriched fractions were isolated from the homogenized rat kidney by differential centrifugation in dextran or sucrose. Marker enzymes and morphological studies indicated that one fraction (BLM) was enriched in membrane particles originating from the basolateral membrane of tubular cells, while the other, the PM fraction, contained membrane from the luminal side. Membrane-bound kallikrein and renin were found in both fractions. Kallikrein activity was enhanced by phospholipase A2, melittin and detergents. Renin activity was greatly increased after solubilization by the same agents. In addition to bound kallikrein and renin BLM contained a prekallikrein which was activated by trypsin or plasmin. BLM prekallikrein has a slower electrophoretic mobility and a higher molecular weight than urinary or glandular kallikrein. The basal membrane of tubular cells appears to contain all of the essential enzyme components of the kallikrein and renin systems. Kallikrein of the PM fraction is probably released into the urine, while prekallikrein and kallikrein from basal membrane may be the source of kallikrein in lymph and renal venous effluent. Membrane-bound renin could be a form of renin retained by the kidney.
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PMID:Prekallikrein, kallikrein and renin in membrane fractions of rat kidney. 675 83

Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression. The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies to PA-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive phenotype, which was again attenuated by MAI-12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell adhesion (IC50 180 nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.
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PMID:Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro. 1159 1