Journalartikel

Jahr der Veröffentlichung: 2007

Seiten: 21671-21682

Zeitschrift: Journal of Biological Chemistry

Bandnummer: 282

Heftnummer: 30

ISSN: 0021-9258

eISSN: 1083-351X

Open Access Status: Green

DOI Link: https://doi.org/10.1074/jbc.M610748200

Verlag: Elsevier

Abstract: 
Factor VII-activating protease (FSAP) is a novel plasma-derived serine protease structurally homologous to tissue-type and urokinase-type plasminogen activators. We demonstrate that plasminogen activator inhibitor-1 (PAI-1), the predominant inhibitor of tissue-type and urokinase-type plasminogen activators in plasma and tissues, is an inhibitor of FSAP as well. We detected PAI-1.FSAP complexes in addition to high levels of extracellular RNA, an important FSAP cofactor, in bronchoal-veolar lavage fluids from patients with acute respiratory distress syndrome. Hydrolytic activity of FSAP was inhibited by PAI-1 with a second-order inhibition rate constant (K-a) of 3.38 +/- 1.12 x 105 M-1.s(-1). Residue Arg(346) was a critical recognition element on PAI-1 for interaction with FSAP. RNA, but not DNA, fragments (>400 nucleotides in length) dramatically enhanced the reactivity of PAI-1 with FSAP, and 4 mu g.ml(-1) RNA increased the K-a to 1.61 +/- 0.94 x 106 M-1.s(-1). RNA also stabilized the active conformation of PAI-1, increasing the half-life for spontaneous conversion of active to latent PAI-1 from 48.4 +/- 8 min to 114.6 +/- 5 min. In contrast, little effect of DNA on PAI-1 stability was apparent. Residues Arg(76) and Lys(80) in PAI-1 were key elements mediating binding of nucleic acids to PAI-1. FSAP-driven inhibition of vascular smooth muscle cell proliferation was antagonized by PAI-1, suggesting functional consequences for the FSAP-PAI-1 interaction. These data indicate that extracellular RNA and PAI-1 can regulate FSAP activity, thereby playing a potentially important role in hemostasis and cell functions under various pathophysiological conditions, such as acute respiratory distress syndrome.

Harvard-Zitierstil: Wygrecka, M., Morty, R., Markart, P., Kanse, S., Andreasen, P., Wind, T., et al. (2007) Plasminogen activator inhibitor-1 is an inhibitor of factor VII-activating protease in patients with acute respiratory distress syndrome, Journal of Biological Chemistry, 282(30), pp. 21671-21682. https://doi.org/10.1074/jbc.M610748200

APA-Zitierstil: Wygrecka, M., Morty, R., Markart, P., Kanse, S., Andreasen, P., Wind, T., Guenther, A., & Preissner, K. (2007). Plasminogen activator inhibitor-1 is an inhibitor of factor VII-activating protease in patients with acute respiratory distress syndrome. Journal of Biological Chemistry. 282(30), 21671-21682. https://doi.org/10.1074/jbc.M610748200