Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
(2008) In Blood 111(6). p.3034-3041- Abstract
- Protein S expresses cofactor activity for activated protein C (APC) by enhancing the APC-catalyzed proteolysis at R-306 in factor Va. It is generally accepted that only free protein S is active and that complex formation with C4b-binding protein (C4BP) inhibits the APC-cofactor activity of protein S. However, the present study shows that protein S-C4BP expresses APC-cofactor activity and stimulates APC-catalyzed proteolysis at R-306 more than 10-fold, but instead inhibits proteolysis at R-506 by APC 3- to 4-fold. Free protein S stimulates APC-catalyzed cleavage at R-306 approximately 20-fold and has no effect on cleavage at R-506. The resulting net effect of protein S-C4BP complex formation on APC-catalyzed factor Va inactivation is a 6-... (More)
- Protein S expresses cofactor activity for activated protein C (APC) by enhancing the APC-catalyzed proteolysis at R-306 in factor Va. It is generally accepted that only free protein S is active and that complex formation with C4b-binding protein (C4BP) inhibits the APC-cofactor activity of protein S. However, the present study shows that protein S-C4BP expresses APC-cofactor activity and stimulates APC-catalyzed proteolysis at R-306 more than 10-fold, but instead inhibits proteolysis at R-506 by APC 3- to 4-fold. Free protein S stimulates APC-catalyzed cleavage at R-306 approximately 20-fold and has no effect on cleavage at R-506. The resulting net effect of protein S-C4BP complex formation on APC-catalyzed factor Va inactivation is a 6- to 8-fold reduction in factor Va inactivation when compared with free protein S, which is not explained by inhibition of APC-cofactor activity of protein S at R306, but by generation of a specific inhibitor for APC-catalyzed proteolysis at R-506 of factor Va. These results are of interest for carriers of the factor V-Leiden mutation (R(506)Q), as protein S-C4BP effectively enhances APC-catalyzed factor Va (R-306) inactivation in plasma containing factor V-Leiden. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1185149
- author
- Maurissen, Lisbeth F A ; Thomassen, M. Christella L G D ; Nicolaes, Gerry A F ; Dahlbäck, Björn LU ; Tans, Guido ; Rosing, Jan and Hackeng, Tilman M
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 111
- issue
- 6
- pages
- 3034 - 3041
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000254009600016
- scopus:42449084553
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2007-06-089987
- language
- English
- LU publication?
- yes
- id
- b40752fa-8e9b-4900-b195-a9a991c52c2b (old id 1185149)
- date added to LUP
- 2016-04-01 12:09:17
- date last changed
- 2022-03-28 21:02:03
@article{b40752fa-8e9b-4900-b195-a9a991c52c2b,
abstract = {{Protein S expresses cofactor activity for activated protein C (APC) by enhancing the APC-catalyzed proteolysis at R-306 in factor Va. It is generally accepted that only free protein S is active and that complex formation with C4b-binding protein (C4BP) inhibits the APC-cofactor activity of protein S. However, the present study shows that protein S-C4BP expresses APC-cofactor activity and stimulates APC-catalyzed proteolysis at R-306 more than 10-fold, but instead inhibits proteolysis at R-506 by APC 3- to 4-fold. Free protein S stimulates APC-catalyzed cleavage at R-306 approximately 20-fold and has no effect on cleavage at R-506. The resulting net effect of protein S-C4BP complex formation on APC-catalyzed factor Va inactivation is a 6- to 8-fold reduction in factor Va inactivation when compared with free protein S, which is not explained by inhibition of APC-cofactor activity of protein S at R306, but by generation of a specific inhibitor for APC-catalyzed proteolysis at R-506 of factor Va. These results are of interest for carriers of the factor V-Leiden mutation (R(506)Q), as protein S-C4BP effectively enhances APC-catalyzed factor Va (R-306) inactivation in plasma containing factor V-Leiden.}},
author = {{Maurissen, Lisbeth F A and Thomassen, M. Christella L G D and Nicolaes, Gerry A F and Dahlbäck, Björn and Tans, Guido and Rosing, Jan and Hackeng, Tilman M}},
issn = {{1528-0020}},
language = {{eng}},
number = {{6}},
pages = {{3034--3041}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation}},
url = {{http://dx.doi.org/10.1182/blood-2007-06-089987}},
doi = {{10.1182/blood-2007-06-089987}},
volume = {{111}},
year = {{2008}},
}