Kinetics of activation and autoactivation of human factor XII

Tankersley, Donald L.; Finlayson, J. S.

doi:10.1021/bi00297a016

Cited by 160 publications

(121 citation statements)

References 26 publications

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“…µg/ml Polybrene that prevented continued factor XII activation, were added and the activity of formed factor XIIa was evaluated by hydrolysis of chromogenic peptide by measuring absorbance at 405 nm (10). The concentration of formed factor XIIa, and hence of hydrolyzed factor XII, was determined by comparison to the velocities of reaction of known concentrations of factor XIIa.…”

Section: Gagsmentioning

confidence: 99%

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

Gozzo

Nunes

Nader

et al. 2003

Braz J Med Biol Res

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Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml) on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4-and 6-sulfates) reduced (1.2 to 3.0 times) the catalytic efficiency of kallikrein (in a nanomolar range) on the hydrolysis of plasminogen (0.3 to 1.8 µM) and increased (1.9 to 7.7 times) the enzyme efficiency in factor XII (0.1 to 10 µM) activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times) kallikrein inhibition by antithrombin (1.4 µM), while chondroitin 4-and 6-sulfates reduced it (1.3 times). Heparin and heparan sulfate increased (1.4 times) the enzyme inhibition by the C1-inhibitor (150 nM).

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Section: Gagsmentioning

confidence: 99%

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

Gozzo

Nunes

Nader

et al. 2003

Braz J Med Biol Res

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“…Kallikrein can, in turn, reciprocally activate FXII. In the absence of a procoagulant surface, however, the kallikrein-dependent activation of FXII is slow and FXII autoactivation is practically not detectable [ 5 ] . Negatively charged surfaces stimulate contact activation significantly.…”

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confidence: 99%

The Surface‐Dependent Autoactivation Mechanism of Factor XII

Røjkjær

Schousboe

1997

European Journal of Biochemistry

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The dependency of concentrations of Zn2+ and the negatively charged surfaces, phosphatidylinositol phosphate (PtdInsP), sulfatide and dextran sulfate, on the autoactivation of human factor XII, has been studied. While the autoactivation induced by sulfatide, and low concentrations of dextran sulfate, was unaffected by the presence of Zn2+, that induced by PtdInsP and higher concentrations of dextran sulfate was completely dependent on Zn2+ : the excess of Zn2+ needed to induce maximal activity with PtdInsP was 12-fold the concentration of factor XII, while with dextran sulfate it was 40-fold. Determination of the Znz+-binding properties of factor XI1 revealed that a total of four zinc ions could bind to each factor XI1 molecule. The first bound zinc ions (Kd 0.1 pM) induced an increase in the intrinsic tryptophan fluorescence of factor XII, while further titration up to a 40-fold surplus resulted in a quenching of the fluorescence. Binding of the zinc ions that caused the quenching had an average Kd of approximately 1 pM, independent of whether it was determined from the fluorescence changes or by equilibrium filtration. Low concentrations of both sulfatide and PtdInsP induced a fluorescence increase similar to that at low concentrations of Zn2+ but, in contrast to sulfatide, higher concentrations of PtdInsP did not induce a quenching in fluorescence. As the Zn2+-independent activating surface (sulfatide) induced quenching in the fluorescence intensity, while the Zn*+-dependent activating surface (PtdInsP) did not, the quenching, whether it was caused by sulfatide or zinc ions, was assigned to a change in the conformation which resulted in a molecular structure of factor XI1 that could be autoactivated. Association of factor XI1 in this conformation on the activating surface was suggested to be responsible for the autoactivation.Keywords: human factor XI1 ; zinc ; autoactivation; negatively charged surfaces ; conformational changes.Factor XI1 (FXII) circulates in normal plasma at a concentration of 30 pg/ml and constitutes, together with prekallikrein and high-molecular-mass kininogen the plasma contact activation system (for reviews see [I-41). It is a monomeric zymogen (80 kDa) that, by a single proteolytic cleavage of the Arg373-Val374 peptide bond within a disulfide loop, is transformed into the serine protease a-factor XIIa (FXIIa). In addition to its function in the contact activation system, it plays a role in the activation of the classical complement pathway as well as in the fibrinolytic system, in the production of kinins and in the initiation of cell-mediated inflammatory responses. By limited proteolysis, FXIIa activates prekallikrein and factor XI1 (autoactivation) and is connected to the intrinsic pathway of coagulation by activation of factor XI. Kallikrein can, in turn, reciprocally activate FXII. In the absence of a procoagulant surface, however, the kallikrein-dependent activation of FXII is slow and FXII autoactivation is practically not detectable [ 5 ] . Negatively charged surfaces stimulat...

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“…There are several possible ex- planations of this result: 1) Pro-PHBP has a weak protease activity, 2) The pro-PHBP preparation contained an undetectable amount of the active hetero-dimer form of PHBP and 3) The pro-PHBP preparation contained an undetectable amount of other protease which cleaves pro-PHBP. These possibilities have been discussed as being involved in the activation mechanism of factor XII, [2][3][4][5][6][7]22) but it is difficult to confirm them at the present time.…”

Section: Discussionmentioning

confidence: 99%

Regulation Mechanism of the Serine Protease Activity of Plasma Hyaluronan Binding Protein.

Choi-Miura

Saito

Takahashi

et al. 2001

Biological & Pharmaceutical Bulletin

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We earlier reported the purification of a novel hyaluronanbinding protein from human plasma with hyaluronan-conjugated Sepharose which we called plasma hyaluronan binding protein (PHBP).1) The result of the sequence analysis of the PHBP cDNA indicated that it has a similar structure to that of hepatocyte growth factor activator (HGFA), the serine protease which cleaves pro-hepatocyte growth factor (HGF) to the active hetero-dimer form. Indeed, we also detected the serine protease activity of PHBP with Boc-Phe-Ser-Argmethylcoumarine amide (MCA) as the synthetic substrate. PHBP was present in serum as the single-chain precursor form (pro-PHBP) of 70 kDa, however, the purified PHBP from human plasma with AC4 (anti-PHBP mouse monoclonal antibody)-conjugated Sepharose contained the singlechain form and some amount of the hetero-dimer form. The hetero-dimer form was composed of the 50-kDa N-terminal heavy chain and the 27-kDa C-terminal light chain, both of which were bridged by a disulfide linkage. During the incubation of the purified PHBP at 37°C, pro-PHBP completely converted to the hetero-dimer form, which possessed the serine protease activity, by auto-cleavage as well as factor XII of the coagulation system. 2-7) These results suggested that the proteases in the coagulation system were not involved in the activation of pro-PHBP and it was different from the activations of factor XII 8-10) and HGFA, 11) which were cleaved and activated during the coagulation. The results also suggested the presence of protease inhibitor which prevents the fragmentation of pro-PHBP in human serum. In this paper, we describe the purification and identification of the inhibitor for the serine protease activity of PHBP and the activation mechanism of pro-PHBP. MATERIALS AND METHODS MaterialsDextran sulfate (molecular weight of 500 kDa) was purchased from Pharmacia Biotech. Bovine brain phosphatidylethanolamine was obtained from Sigma. Kaolin was from Wako Pure Chemicals.Purification of the Active Form and the Precursor Form of PHBP The active hetero-dimer form of PHBP was purified from human plasma as described previously with AC4 (anti-PHBP mouse monoclonal antibody)-conjugated Sepharose. Briefly, human plasma (500 ml) was applied to the column of AC4-Sepharose (1 mg IgG/ml Sepharose, 50 ml). After washings with 0.5 M NaCl in 10 mM sodium phosphate, pH 7.0 (500 ml) and distilled water (100 ml), the bound proteins were eluted with 0.2 M glycine-HCl, pH 2.5. After neutralization with 1 M Tris, the contaminating IgG was removed by passing it through the column of anti-human IgG rabbit antibody-conjugated Sepharose. The single-chain precursor form of PHBP (pro-PHBP) was purified by the same procedure with the exception that every solution contained 1 mg/ml of FUT-175 (Torii Pharmaceutical Co.). The Pro-PHBP preparation was dialyzed against PBS to remove FUT-175 at 4°C overnight.Measurement of the Inhibitor Activity or the Activator Activity for PHBP To measure the inhibitor activity for PHBP, the active form of PHBP (700 ng) was incuba...

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Kinetics of activation and autoactivation of human factor XII

Cited by 160 publications

References 26 publications

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

The Surface‐Dependent Autoactivation Mechanism of Factor XII

Regulation Mechanism of the Serine Protease Activity of Plasma Hyaluronan Binding Protein.

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