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Thromb Haemost 2000; 83(05): 709-714
DOI: 10.1055/s-0037-1613897
Review Article
Schattauer GmbH

High Molecular Weight Kininogen Is Cleaved by FXIa at Three Sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326

T. Mauron
1   From the Central Hematology Laboratory, University of Bern, Inselspital, Bern, Switzerland
,
B. Lämmle
1   From the Central Hematology Laboratory, University of Bern, Inselspital, Bern, Switzerland
,
W. A. Wuillemin
1   From the Central Hematology Laboratory, University of Bern, Inselspital, Bern, Switzerland
› Author AffiliationsThe present work was supported by a grant from the Swiss National Foundation for Scientific Research (no 3200-055312.98). We appreciate the assistance of Dr. J. Schaller and U. Kempfer of the University of Bern in the performance of the amino acid sequence analysis. We also wish to thank Isabelle Aebi-Huber for technical assistance.
Further Information

Publication History

Received 07 July 1999

Accepted after resubmission 21 December 1999

Publication Date:
08 December 2017 (online)

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Summary

We investigated the cleavage of high molecular weight kininogen (HK) by activated coagulation factor XI (FXIa) in vitro. Incubation of HK with FXIa resulted in the generation of cleavage products which were subjected to SDS-Page and analyzed by silverstaining, ligandblotting and immunoblotting, respectively. Upon incubation with FXIa, bands were generated at 111, 100, 88 kDa on nonreduced and at 76, 62 and 51 kDa on reduced gels. Amino acid sequence analysis of the reaction mixtures revealed three cleavage sites at Arg409-Arg410, at Lys502-Thr503 and at Lys325-Lys326. Analysis of HK-samples incubated with FXIa for 3 min, 10 min and 120 min indicated HK to be cleaved first at Arg409-Arg410, followed by cleavage at Lys502-Thr503 and then at Lys325-Lys326.

In conclusion, HK is cleaved by FXIa at three sites. Cleavage of HK by FXIa results in the loss of the surface binding site of HK, which may constitute a mechanism of inactivation of HK and of control of contact system activation.

Key words

Factor XIa - high molecular weight kininogen - contact activation - cleavage site
 

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