Procoagulant activity of high molecular weight kininogen light chain deletion mutants.

1993 ◽  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Light Chain ◽  
Procoagulant Activity ◽  
Deletion Mutants ◽  
High Molecular Weight Kininogen

Corrections - High Molecular Weight Kininogen or its Light Chain Protects Human Plasma Kallikrein from Inactivation by Plasma Protease Inhibitors

Biochemistry ◽  
1982 ◽  
Vol 21 (12) ◽  
pp. 3036-3036
Author(s):  
Marc Schapira ◽  
Cheryl Scott ◽  
Ann James ◽  
Lee Silver ◽  
Frederich Kueppers ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Light Chain ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen

scholarly journals Relationship between structure and correcting activity of bovine high molecular weight kininogen upon the clotting time of fitzgerald-trait plasma

1979 ◽  
Vol 149 (4) ◽  
pp. 847-855 ◽  
Author(s):  
AG Scicli ◽  
R Waldmann ◽  
JA Guimaraes ◽  
G Scicli ◽  
OA Carretero ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Heavy Chain ◽  
Light Chain ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen ◽  
Clotting Time ◽  
Active Inhibitor ◽  
Charged Surfaces ◽  
Bovine Plasma

Bovine high molecular weight kininogen (bHMWK) partially corrects the activated plasma thromboplastin time (aPTT) of Fitzgerald trait plasma which is congenitally deficient in HMWK. The relationship between the structure and activity of HMWK was clarified by studying the effects of different fragments of bHMWK on the aPTT of Fitzgerald-trait plasma. The peptides studied were lys-bradykinin-free HMWK, bradykinin-fragment 1-2-free HMWK, heavy chain, fragment 1-2-light chain, and light chain. All fragments were tested in equimolar concentrations. Bradykinin-fragment 1-2-free HMWK, heavy chain, and light chain have little or no correcting activity upon Fitzgerald-trait plasma aPTr. Fragment 1-2 light chain has the same correcting activity as intact bHMWK, while that of lys-bradykinin-free HMWK appears to be higher. Both fragment 1-2 and fragment 2 inhibit the clotting time of normal human plasma. When compared on a molar basis, fragment 2 is a more active inhibitor than fragment 1-2. When the effects of bovine plasma kallikrein upon bHMWK and hHMWK were studied, it was found that it released kinins from both kininogens. However, while the correcting activity of bHMWK was completely destroyed after 60 min of incubation, that of hHMWK was fully retained. These data suggest that: (a) the active part of bHMWK is comprised of the fragment 1-2 light chain portion; (b) fragment 1-2 or fragment 2 is the binding site to negatively charged surfaces, while the light chain interacts with other components of the surface-mediated reactions; and (c) bovine plasma kallikrein releases kinins, but probably does not cause the release of fragment 1-2 from human HMWK.

scholarly journals Relationship of contact activation cofactor (CAC) procoagulant activity to kininogen

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 935-945 ◽  
Author(s):  
S Schiffman ◽  
P Lee ◽  
DI Feinstein ◽  
R Pecci
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Procoagulant Activity ◽  
Antigenic Determinants ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Precipitin Line ◽  
A Site ◽  
Relationship Of ◽  
The Relationship

Abstract Contact activation cofactor (CAC) facilitates the interaction of factors XI and XII. Patients lacking CAC have a coagulation defect and are deficient in high molecular weight kininogen. The coincidence of these two defects suggests that a single protein may be responsible for both physiologic functions. Immunologic and activity studies have been made on isolated CAC to clarify the relationship between CAC and kininogen. CAC forms a single precipitin line with anti-human kininogen, and antikininogen neutralizes CAC activity. CAC and high molecular weight kininogen show a reaction of identity on immunodiffusion against rabbit anti-CAC. Anti-CAC forms two precipitin lines with normal plasma which can be identified as high and low molecular weight kininogen. Monospecific immunoabsorbed anti-CAC forms a single precipitin line with plasma high molecular weight kininogen and neutralizes CAC activity. Cleavage of kinin fragment from CAC by insoluble trypsin or kalikrein does not proportionally reduce procoagulant activity. CAC neutralized by anti-CAC can release kinins on exposure to trypsin or kallikrein. The results support the conclusions that CAC procoagulant activity is a function of high molecular weight kininogen, that antigenic determinants unique to high molecular weight kininogen are shared by the CAC portion of the molecule, and that the clotting reactions may occur at a site removed from the kinin peptide.

scholarly journals Characterization of the procoagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 457-463 ◽  
Author(s):  
M Maier ◽  
KF Austen ◽  
J Spragg
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Broad Band ◽  
Limited Proteolysis ◽  
Procoagulant Activity ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen ◽  
Single Chain ◽  
Amino Terminal ◽  
A Chain

Abstract Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant (“light”) chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of “heavy” and “light” chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C- chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions.

scholarly journals An essential role of high-molecular-weight kininogen in endotoxemia

2017 ◽  
Vol 214 (9) ◽  
pp. 2649-2670 ◽  
Author(s):  
Aizhen Yang ◽  
Zhanli Xie ◽  
Bo Wang ◽  
Robert W. Colman ◽  
Jihong Dai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Light Chain ◽  
Essential Role ◽  
High Molecular Weight Kininogen ◽  
Core Oligosaccharide ◽  
E Coli ◽  
Chain Form ◽  
Deficient Mice

In this study, we show that mice lacking high-molecular-weight kininogen (HK) were resistant to lipopolysaccharide (LPS)-induced mortality and had significantly reduced circulating LPS levels. Replenishment of HK-deficient mice with human HK recovered the LPS levels and rendered the mice susceptible to LPS-induced mortality. Binding of HK to LPS occurred through the O-polysaccharide/core oligosaccharide, consistent with the ability to bind LPS from K. pneumoniae, P. aeruginosa, S. minnesota, and different E. coli strains. Binding of LPS induced plasma HK cleavage to the two-chain form (HKa, containing a heavy chain [HC] and a light chain [LC]) and bradykinin. Both HKa and the LC, but not the HC, could disaggregate LPS. The light chain bound LPS with high affinity (Kd = 1.52 × 10−9 M) through a binding site in domain 5 (DHG15). A monoclonal antibody against D5 significantly reduced LPS-induced mortality and circulating LPS levels in wild-type mice. Thus, HK, as a major LPS carrier in circulation, plays an essential role in endotoxemia.

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