Document Detail


Protein S Thr103Asn mutation associated with type II deficiency reproduced in vitro and functionally characterised.
MedLine Citation:
PMID:  11019964     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protein S functions as a cofactor to activated protein C (APC) in the degradation of FVa and FVIIIa. In protein S, the thrombin sensitive region (TSR) and the first EGF-like domain are important for expression of the APC cofactor activity. A naturally occurring Thr103Asn (T103N) mutation in the first EGF-like domain of protein S has been associated with functional (type II) protein S deficiency. To elucidate the functional consequences of the T103N mutation, recombinant protein S mutant was expressed in mammalian cells and functionally characterised. The expression level of protein S T103N from transiently transfected COS 1 cells was equal to that of wild type protein S. The mutant protein S and wild type protein S were also expressed in 293 cells after stable transfection, and the recombinant proteins purified. In APTT- and PT-based coagulation assays, the mutant protein demonstrated approximately 50% lower anticoagulant activity as compared to wild type protein S. The functional defect was further investigated in FVa- and FVIIIa-degradation assays. The functional defect of mutant protein S was attenuated at increasing concentrations of APC. The results demonstrate the region around residue 103 of protein S to be of functional importance, possibly through a direct interaction with APC.
Authors:
T K Giri; P García de Frutos; B Dahlbäck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  84     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  413-9     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Lund University, University Hospital Malmö, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
Blood Coagulation Tests
COS Cells
Dose-Response Relationship, Drug
Factor V / drug effects,  metabolism
Factor VIIIa / drug effects,  metabolism
Factor Va / drug effects,  metabolism
Humans
Immunoblotting
Mutagenesis, Site-Directed
Partial Thromboplastin Time
Point Mutation
Protein C / metabolism,  pharmacology
Protein S / genetics*,  pharmacology*
Protein S Deficiency / genetics*
Reagent Kits, Diagnostic
Recombinant Proteins / genetics
Transfection
Chemical
Reg. No./Substance:
0/Protein C; 0/Protein S; 0/Reagent Kits, Diagnostic; 0/Recombinant Proteins; 0/factor V Leiden; 65522-14-7/Factor Va; 72175-66-7/Factor VIIIa; 9001-24-5/Factor V

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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