Author
Marie Johannessen
Bio: Marie Johannessen is an academic researcher. The author has contributed to research in topics: Plasminogen activator & Plasmin. The author has an hindex of 2, co-authored 2 publications receiving 114 citations.
Papers
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TL;DR: The results were interpreted to mean that fibrin binding can induce an activated state of the intact tPA one-chain form, also when plasmin is generated as a result of a plAsminogen activation reaction.
72 citations
TL;DR: The hypothesis that lysine residues 277 or 416 may be involved in stabilization of an active conformation of one-chain t-PA via salt-bridge formation with aspartic acid residue 477 was tested by site-directed mutagenesis.
Abstract: In contrast to most other serine proteases, tissue-type plasminogen activator (t-PA) possesses enzymatic activity as the one-chain zymogen form. The hypothesis that lysine residues 277 or 416 may be involved in stabilization of an active conformation of one-chain t-PA via salt-bridge formation with aspartic acid residue 477 was tested by site-directed mutagenesis. Four recombinant t-PA mutants were constructed. The amidolytic activities of these analogues were compared to that of authentic t-PA. Substitution of arginine-275 provided an analogue [( R275G]t-PA) resistant to plasmin cleavage. The amidolytic activity of [R275G]t-PA was comparable to that of authentic one-chain t-PA, and so was the activity of [R275L,K277L]t-PA, in which additional substitution of lysine residue 277 was carried out. This suggested that its presence was nonessential for obtaining one-chain t-PA activity. In contrast, substitution of lysine residue 416 to obtain [K416S]t-PA and [K416S,H417T]t-PA resulted in substantial quenching of amidolytic one-chain activity. As expected, the amidolytic activities of the two-chain forms were less affected by the substitution. Involvement of lysine residue 416 in one-chain t-PA activity was also indicated by decreased activities of [K416S]t-PA and [K416S,H417T]t-PA with plasminogen as the substrate. The one-chain activity of the lysine residue 416 substitution analogues was partially restored in the presence of fibrin. This could indicate that strong ligands such as fibrin might provide an alternative stabilization of the active conformation of one-chain t-PA.
43 citations
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TL;DR: This work has shown that the protease Nexin I antagonist acts as a “spatially aggregating force” to drive down the activity of the plasminogen during the courtship process.
Abstract: PLASMINOGEN ACTIVATOR INHIBITORS 104 Plasminogen Activator Inhibitor 1 104 Plasminogen Activator Inhibitor 2 106 Protease Nexin I .... .... 108 PHYSIOLOGICAL FUNCTIONS OF PLASMINOGEN ACTIVATION ........ 109 Matrix Breakdown 109 Cell Migration 111 Ovulation 113 CONCLUDING REMARKS 115
877 citations
TL;DR: One-chain u-PA has a variety of properties similar to the one-chain proenzyme forms of other serine proteases and that it should, therefore, be considered as a genuine proen enzyme form of U-PA.
241 citations
TL;DR: Variants of tPA were found that had reduced activity with respect to each tested property; in a few cases increased activity was observed, and a model of the tPA protease domain has been used to map some of the critical residues and regions.
217 citations
TL;DR: Bat-PA(H), the full-length form, is the only Bat-PA species which binds tightly to fibrin, although each of the three species exhibit remarkable stimulation by a fibrIn cofactor.
169 citations
162 citations