@article{0d8e11f062da11ddb1a1000ea68e967b,
title = "Furin proteolytically processes the heparin-binding region of extracellular superoxide dismutase.",
abstract = "Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that attenuates brain and lung injury from oxidative stress. A polybasic region in the carboxyl terminus distinguishes EC-SOD from other superoxide dismutases and determines EC-SOD's tissue half-life and affinity for heparin. There are two types of EC-SOD that differ based on the presence or absence of this heparin-binding region. It has recently been shown that proteolytic removal of the heparin-binding region is an intracellular event (Enghild, J. J., Thogersen, I. B., Oury, T. D., Valnickova, Z., Hojrup, P., and Crapo, J. D. (1999) J. Biol. Chem. 274, 14818-14822). By using mammalian cell lines, we have now determined that removal of the heparin-binding region occurs after passage through the Golgi network but before being secreted into the extracellular space. Specific protease inhibitors and overexpression of intracellular proteases implicate furin as a processing protease. In vitro experiments using furin and purified EC-SOD suggest that furin proteolytically cleaves EC-SOD in the middle of the polybasic region and then requires an additional carboxypeptidase to remove the remaining lysines and arginines. A mutation in Arg(213) renders EC-SOD resistant to furin processing. These results indicate that furin-dependent processing of EC-SOD is important for determining the tissue distribution and half-life of EC-SOD.",
keywords = "Amino Acid Sequence, Animals, Arginine, Blotting, Western, Brefeldin A, CHO Cells, Cell Line, Cricetinae, Electrophoresis, Polyacrylamide Gel, Enzyme Inhibitors, Furin, Glycine, Golgi Apparatus, Heparin, Humans, Mass Spectrometry, Mice, Molecular Sequence Data, Mutation, Oxidative Stress, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Protein Synthesis Inhibitors, Rats, Subtilisins, Superoxide Dismutase, Temperature, Time Factors, Tissue Distribution, Tumor Cells, Cultured",
author = "Bowler, \{Russell P\} and Mike Nicks and Olsen, \{Dorte Aa\} and Th{\o}gersen, \{Ida B\} and Zuzana Valnickova and Peter H{\o}jrup and Alex Franzusoff and Enghild, \{Jan J\} and Crapo, \{James D\}",
year = "2002",
month = may,
day = "10",
doi = "10.1074/jbc.M105409200",
language = "English",
volume = "277",
pages = "16505--11",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "Elsevier",
number = "19",
}