Imperial College London
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Emeritus Professor David Lane

Faculty of Medicine, Department of Immunology and Inflammation

Emeritus Professor of Haematology
 
 
 
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Contact

 

+44 (0)20 3313 2295d.lane

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Reglinska-Matveyev:2014:10.1182/blood-2014-01-551812,
author = {Reglinska-Matveyev, N and Andersson, HM and Rezende, SM and Dahlback, B and Crawley, JTB and Lane, DA and Ahnstroem, J},
doi = {10.1182/blood-2014-01-551812},
journal = {Blood},
pages = {3979--3987},
title = {TFPI cofactor function of protein S: essential role of the protein S SHBG-like domain},
url = {http://dx.doi.org/10.1182/blood-2014-01-551812},
volume = {123},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Protein S is a cofactor for tissue factor pathway inhibitor (TFPI), accelerating the inhibition of activated factor X (FXa). TFPI Kunitz domain 3 residue Glu226 is essential for enhancement of TFPI by protein S. To investigate the complementary functional interaction site on protein S, we screened 44 protein S point, composite or domain swap variants spanning the whole protein S molecule for their TFPI cofactor function using a thrombin generation assay. Of these variants, two protein S/growth arrest–specific 6 chimeras, with either the whole sex hormone–binding globulin (SHBG)-like domain (Val243-Ser635; chimera III) or the SHBG laminin G-type 1 subunit (Ser283-Val459; chimera I), respectively, substituted by the corresponding domain in growth arrest–specific 6, were unable to enhance TFPI. The importance of the protein S SHBG-like domain (and its laminin G-type 1 subunit) for binding and enhancement of TFPI was confirmed in FXa inhibition assays and using surface plasmon resonance. In addition, protein S bound to C4b binding protein showed greatly reduced enhancement of TFPI-mediated inhibition of FXa compared with free protein S. We show that binding of TFPI to the protein S SHBG-like domain enables TFPI to interact optimally with FXa on a phospholipid membrane.
AU  - Reglinska-Matveyev,N
AU  - Andersson,HM
AU  - Rezende,SM
AU  - Dahlback,B
AU  - Crawley,JTB
AU  - Lane,DA
AU  - Ahnstroem,J
DO  - 10.1182/blood-2014-01-551812
EP  - 3987
PY  - 2014///
SN  - 0006-4971
SP  - 3979
TI  - TFPI cofactor function of protein S: essential role of the protein S SHBG-like domain
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood-2014-01-551812
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000342617800022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://ashpublications.org/blood/article/123/25/3979/32901/TFPI-cofactor-function-of-protein-S-essential-role
VL  - 123
ER  -
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