| Protein S Thr103Asn mutation associated with type II deficiency reproduced in vitro and functionally characterised. | |
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MedLine Citation:
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PMID: 11019964 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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T K Giri; P García de Frutos; B Dahlbäck |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Thrombosis and haemostasis Volume: 84 ISSN: 0340-6245 ISO Abbreviation: Thromb. Haemost. Publication Date: 2000 Sep |
Date Detail:
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Created Date: 2001-01-08 Completed Date: 2001-03-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7608063 Medline TA: Thromb Haemost Country: GERMANY |
Other Details:
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Languages: eng Pagination: 413-9 Citation Subset: IM |
Affiliation:
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Department of Laboratory Medicine, Lund University, University Hospital Malmö, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
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