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)

Previous studies established the existence of an FSH-inducible rat granulosa cell-derived insulin-like growth factor binding protein (IGFBP)-5 endopeptidase. It was the objective of this communication to characterize this activity in some detail. Exposure of [125I]rhIGFBP-5 substrate to media conditioned by FSH-treated granulosa cells (a cell-free assay) produced two rhIGFBP-5 cleavage products (estimated size 19.5 and 17.5 kDa). The acquisition of IGFBP-5 endopeptidase activity in culture proved FSH (or PMSG) to be dose and time dependent. The addition of oFSH or rhFSH to the cell-free assay in turn, proved without effect on IGFBP-5 endopeptidase activity, thereby arguing against the possibility of an FSH receptor-independent phenomenon or of contaminating pituitary-derived contribution. The ability of FSH to induce IGFBP-5 endopeptidase activity proved relatively specific in that other granulosa cell agonists such as activin-A, IGF-I, GnRH, interleukin-1beta, TNF alpha, TGF beta1, EGF, or endothelin-1 failed to do so. However, the concurrent provision of GnRH, TNF alpha, EGF, or endothelin-1 proved inhibitory to the IGFBP-5 endopeptidase-inducing property of FSH. Activin-A and TGF beta1 in turn further stimulated the FSH effect. Sensitivity to EDTA, 1,10 phenanthroline, and high concentrations (> or = 0.1 mM) of Zn2+ suggested a Zn2+ metalloprotease. Insensitivity to TIMP-1 and TIMP-2 argued against a matrix metalloprotease (MMP). Relative insensitivity to PMSF, AMPSF, aprotinin, TPCK, and benzamidine argued against the possibility of a serine protease. Insensitivity to pepstatin A and E64 argued against aspartic and cysteine proteases, respectively. Insensitivity to plasminogen activator inhibitor-1 (PAI-1) and the presumed lack of free plasminogen in serum-free culture media argued against plasmin. Proteolysis was completely inhibited over the acid pH range but proceeded unencumbered at neutral and basic pH. Competition studies using unlabeled IGFBPs (1-6) as well as cell-free proteolysis assays of [125I]-labeled IGFBP-1, 2, 3, and 6 suggested a significant level of specificity for the FSH-induced/IGFBP-5-directed endopeptidase. Centricon-mediated fractionation of FSH-conditioned media revealed the IGFBP-5 endopeptidase activity in the fraction representing proteins of molecular weight >100K. Taken together, these observations document a secreted, granulosa cell-derived, high molecular weight, FSH-inducible, IGFBP-5-selective, neutral/basic pH-favoring, non-MMP Zn2+ metalloprotease.
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PMID:Characterization and hormonal regulation of a rat ovarian insulin-like growth factor binding protein-5 endopeptidase: an FSH-inducible granulosa cell-derived metalloprotease. 949 60

Protease nexin-1 (PN-1)/glia-derived nexin (GDN) is a member of the Serpin (serine proteinase inhibitor) family, and can inhibit thrombin, plasmin, and plasminogen activators. PN-1 has been shown to be a neuroprotective factor in a number of assay systems, and this activity has been assumed to be a function of its protease inhibitory function. Here, we report cloning and characterization of a Xenopus orthologue of PN-1 (xPN-1). xPN-1 was isolated in a functional screen of an egg cDNA library for factors that modify early axial patterning. xPN-1 is expressed maternally through late tadpole stages, and is expressed preferentially in the notochord, the pharyngeal endoderm, the otic vesicle, and the ventral region of the brain in tailbud embryos. Over-expression of xPN-1 causes defective gastrulation, inhibits convergent extension movements in activin induced animal caps, and inhibits expression of a distinct subset of activin induced mesendodermal markers. Interestingly, expression of point or deletion mutation of the Reactive Center Loop of xPN1,which is essential for the protease inhibitory activity of all serpins, had effects on Xenopus development indistinguishable from those of wild type xPN-1. These observations suggest the possibility that xPN-1 has a novel activity in addition to its established function as an inhibitor of serine proteases.
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PMID:A Serpin family gene, protease nexin-1 has an activity distinct from protease inhibition in early Xenopus embryos. 1679 67