ライフサイエンスコーパス: factor XI

1 quired for hepatocyte-specific expression of factor XI.

2 weight kininogen (HK31-mer) can also bind to factor XI.

3 the gene for the blood coagulation protease factor XI.

4 K(m) 35-fold greater than that of wild-type factor XI.

5 bstrate of the intrinsic coagulation pathway factor XI.

6 with HK for binding to the Apple 1 domain of factor XI.

7 agonists in the absence of detectable plasma factor XI.

8 activation-dependent expression of platelet factor XI.

9 5,000 reduced) different from that of plasma factor XI.

10 these exons was identical to that of plasma factor XI.

11 mpared its properties with human recombinant factor XI.

12 f 624 amino acids with 78% homology to human factor XI.

13 for an increased prekallikrein and decreased factor XI.

14 ogical significance of the dimeric nature of factor XI.

15 ntity and a domain structure very similar to factor XI.

16 nt-like Apetela 2 (AP2) domain transcription factor XI-3 (AP2XI-3), not present in human cells, was c

17 iltered platelets promoted the activation of factor XI (60 nm) by thrombin (0.02-10 nm, EC(50) approx

18 A12 and 11AE) that recognize epitopes on the factor XI A3 domain were potent inhibitors of factor IX

19 , factor IX, in an interaction requiring the factor XI A3 domain.

20 hysiological concentration of prekallikrein, factor XI abrogates HK binding to HUVEC in a concentrati

21 The maximum rates of factor XI activation achieved in the presence of activat

22 port that polyphosphate potently accelerates factor XI activation by alpha-thrombin, beta-thrombin, a

23 ompared with dextran sulfate as surfaces for factor XI activation by factor XIIa, factor XIa, or thro

24 ion of fibrinogen (9.0 micrometer) inhibited factor XI activation by thrombin (but not by factor XIIa

25 Activated gel-filtered platelets promoted factor XI activation by thrombin at initial rates 2-5-fo

26 ical concentrations of HK (636 nM) inhibited factor XI activation by thrombin in a concentration-depe

27 binding to lipid rafts, and initial rates of factor XI activation by thrombin on activated platelets

28 estigated whether glycocalicin could promote factor XI activation by thrombin, another GP Ibalpha lig

29 mers and surfaces have been shown to enhance factor XI activation by thrombin, the physiologic cofact

30 brin clot structure, and greatly accelerates factor XI activation by thrombin.

31 that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the

32 ons (360 nm), the rate of thrombin-catalyzed factor XI activation in the presence of glycocalicin was

33 ts and platelet-mediated, thrombin-catalyzed factor XI activation in the presence of prothrombin and

34 n in the factor XI experiment indicates that factor XI activation occurs exclusively by thrombin.

35 romoting optimal rates of thrombin-catalyzed factor XI activation on the platelet surface, thereby in

36 act pathway and amplified thrombin-dependent factor XI activation.

37 sulfate as a surface for thrombin-catalyzed factor XI activation.

38 tors XIIa and XIa, thrombin is the preferred factor XI activator, and activated platelets are a relev

39 All adults tested for factor XI activity between 2002 and 2014 were included i

40 Factor XI activity was classified into 3 categories: nor

41 3 included patients, 8958 (88.9%) had normal factor XI activity, 690 (6.8%) had mild deficiency, and

42 ied thrombin as the most likely activator of factor XI, although this reaction is slow in solution.

43 ids are located in the third apple domain of factor XI, an area implicated in binding interactions wi

44 n of the naturally occurring complex between factor XI and HK by the addition of a 31-amino acid pept

45 atelets by the recombinant Apple 3 domain of factor XI and inhibition by unlabeled factor XI were ide

46 n at various concentrations exposed platelet factor XI and PAC1 antibody binding in parallel.

47 fective as the recombinant Apple 3 domain of factor XI and unlabeled factor XI in inhibiting [(125)I]

48 kallikrein, high-molecular weight kininogen, factor XI, and factor XII were decreased in the disease-

49 The zymogen, factor XI, and the enzyme, factor XIa, interact specific

50 Flow cytometry with an affinity-purified factor XI antibody, with PAC1 antibody (to the GPIIb/III

51 Both recombinant murine and human factor XI are 160 kD homodimers comprised of two 80 kD p

52 results indicate that two forms of activated factor XI are generated during coagulation, and that eac

53 site of synthesis and the nature of platelet factor XI are not known.

54 in fragment 2 binds to the Apple 1 domain of factor XI at or near the site where high molecular weigh

55 Only activated platelets supported factor XI binding in the presence of HK and zinc (K(D) =

56 Here, we provide evidence that the factor XI binding site on platelets is in the glycoprote

57 tide analogue of this sequence inhibits both factor XI binding to activated platelets and platelet-me

58 Inhibition of [(125)I]factor XI binding to activated platelets by the recombin

59 nd unlabeled factor XI in inhibiting [(125)I]factor XI binding to activated platelets.

60 c peptides were used to compete with [(125)I]factor XI binding to activated platelets.

61 Apple 3 domain of factor XI, which mediates factor XI binding to platelets, also completely displace

62 M), and CaCl2 (2 mM), conditions optimal for factor XI binding to platelets.

63 located in the Apple 3 domain which mediates factor XI binding to platelets.

64 kininogen (and Zn2+), which are required for factor XI binding to platelets.

65 y) and bovine von Willebrand factor, inhibit factor XI binding to platelets; 3) by surface plasmon re

66 An antibody to GPIb (SZ-2) that disrupts factor XI binding to the GPIb-IX-V complex also disrupte

67 ed in von Willebrand's factor secretion, but factor XI binding was not observed.

68 elets, lacking the complex, are deficient in factor XI binding; 2) two GP Ibalpha ligands, SZ-2 (a mo

69 ion of a 31-amino acid peptide mimicking the factor XI-binding site on HK restored HK binding to HUVE

70 Factor XI binds to activated platelets where it is effic

71 Factor XI binds to high affinity sites on the surface of

72 In microtiter wells factor XI binds to more sites in the absence of HUVEC (1

73 Thus, factor XI binds to the GP Ib-IX-V complex, promoting its

74 platelets; 3) by surface plasmon resonance, factor XI bound specifically to glycocalicin (the extrac

75 Interestingly, zymogen factor XI bound SPGG with high affinity, suggesting its

76 xpressed approximately 40% of total platelet factor XI but no PAC1 binding sites.

77 n, because ADP and collagen exposed platelet factor XI but no S12 binding sites.

78 prekallikrein is structurally homologous to factor XI, but activated factor IX poorly.

79 ccelerate thrombin activation of coagulation factor XI by a template mechanism.

80 is important for promoting the activation of factor XI by thrombin on the platelet surface.

81 tease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a cr

82 Factor XI cDNA was cloned from a megakaryocyte library a

83 Factor XI circulates as a homodimer, and the presence of

84 terminus of the A3 domain markedly decreased factor XI coagulant activity.

85 Variants of factor XI containing Gln226 to Arg (Q226 to R) and Ser24

86 This study showed that factor XI contributes to postoperative venous thromboemb

87 Platelets from four patients with plasma factor XI deficiency (<0.04 U/mL) had normal constitutiv

88 The incidence of VTE was lower in those with factor XI deficiency (activity <50%) compared with those

89 Factor XI deficiency (MIM 264900) is an autosomal bleedi

90 a 9-year-old boy (the propositus) with mild factor XI deficiency and his mother.

91 Factor XI deficiency is associated with a bleeding diath

92 In summary, factor XI deficiency is associated with decreased incide

93 Factor XI deficiency is one of the rare inherited coagul

94 The data demonstrate that factor XI deficiency results in significantly delayed cl

95 preparation for developing a mouse model of factor XI deficiency to facilitate investigations into t

96 died 39 consecutively referred patients with factor XI deficiency to identify the molecular defect.

97 ns at the FXI locus, which cause coagulation factor XI deficiency, have high frequencies in Jewish po

98 tudies have shown the causative mutations of factor XI deficiency, outside the Ashkenazi Jewish popul

99 e gene deletion as the causative mutation of factor XI deficiency, the result of unequal homologous r

100 rlying cardiovascular benefit may exist with factor XI deficiency.

101 the reaction was more strongly influenced by factor XI deficiency.

102 ion in a patient with subsequently diagnosed factor XI deficiency.

103 CI, 0.35-0.93) in those with moderate-severe factor XI deficiency.

104 actor XI shortens the clotting time of human factor XI deficient plasma in an activated partial throm

105 At the same level of TF in factor XI-deficient blood (XI:C <2%), only minor differe

106 lease of platelet osteonectin were slower in factor XI-deficient blood than in normal blood.

107 Well-washed platelets from normal and from factor XI-deficient donors incubated with low concentrat

108 lood from normal, factor VIII-deficient, and factor XI-deficient donors.

109 ilar to fibrin(ogen)-deficient mice, whereas factor XI-deficient mice show wild-type levels of resist

110 corrected the clotting defect observed with factor XI-deficient plasma.

111 Factor XI did not bind to HUVEC or to HEK293 cell monola

112 In the absence of coagulation inhibitors, factor XI did not influence thrombin generation initiate

113 Murine factor XI differs from human factor XI in that it underg

114 Because factor XI displays both procoagulant and antifibrinolyti

115 These results, consistent with previous factor XI domain analyses, suggest that the active site

116 actor XIa generation by added hirudin in the factor XI experiment indicates that factor XI activation

117 , we cloned the complementary DNA for murine factor XI, expressed the protein in a mammalian expressi

118 Activated factor XI (factor XIa) participates in blood coagulation

119 Activated coagulation factor XI (factor XIa) proteolytically cleaves its subst

120 their mean values for prothrombin, factor X, factor XI, factor IX, factor VII, factor VIII, factor V,

121 Genes for the "contact system" factors (factor XI, factor XII, and prekallikrein) could not be i

122 ding to platelets, also completely displaces factor XI from membrane rafts.

123 In this study, we tested the hypothesis that factor XI (FXI) activation occurs in plasma following ac

124 h both proteins bind, we examined binding of factor XI (FXI) and FXIa to heparin.

125 Thrombin, generated through activation of factor XI (FXI) and/or tissue factor (TF)-factor VIIa, i

126 Mice lacking factor XII (fXII) or factor XI (fXI) are resistant to experimentally-induced

127 Factor XI (FXI) binds specifically and reversibly to hig

128 We have previously shown that the zymogen factor XI (FXI) binds to activated platelets but not to

129 on thrombin production of the activation of factor XI (fXI) by thrombin and of the activation of fac

130 Activation of factor XI (FXI) by thrombin on stimulated platelets play

131 teases factor XII (FXII), prekallikrein, and factor XI (FXI) can trigger coagulation and inflammatory

132 The blood coagulation protein factor XI (FXI) consists of a pair of disulfide-linked c

133 The plasma zymogens factor XII (fXII) and factor XI (fXI) contribute to thrombosis in a variety of

134 Factor XI (FXI) contributes substantially to pathologica

135 Individuals with Factor XI (FXI) deficiency have a variable bleeding tend

136 Factor XI (FXI) deficiency is an autosomal bleeding diso

137 leeding diathesis associated with hereditary factor XI (fXI) deficiency is prevalent in Ashkenazi Jew

138 The bleeding disorder associated with factor XI (fXI) deficiency is typically inherited as an

139 Coagulation factor XI (FXI) has become increasingly interesting for

140 nces several reactions involving coagulation factor XI (FXI) including activation of FXI by factor XI

141 Coagulation factor XI (FXI) is a covalent homodimer consisting of tw

142 Factor XI (FXI) is a homodimeric blood coagulation prote

143 Factor XI (FXI) is a homodimeric plasma zymogen that is

144 Factor XI (fXI) is a homodimeric zymogen that is convert

145 Human coagulation factor XI (FXI) is a plasma serine protease composed of

146 Factor XI (FXI) is the zymogen of an enzyme (FXIa) that

147 Factor XI (FXI) is the zymogen of FXIa, which cleaves FI

148 sis associated with congenital deficiency of factor XI (FXI) is variable and correlates poorly with s

149 Activation of coagulation factor XI (FXI) may play a role in hemostasis.

150 Coagulation factor XI (FXI) plays an important part in both venous a

151 vitro, activated factor XII (fXIIa) converts factor XI (fXI) to fXIa.

152 eficiency of the coagulation serine protease factor XI (FXI) was reported to be homozygous for a Gly(

153 The Apple 4 (A4) domain of human plasma factor XI (FXI) was used to investigate the process of F

154 -Willebrand-factor antigen and activity, and factor XI (FXI) were measured in all patients; further t

155 eeding may be possible through inhibition of factor XI (FXI), a component of the intrinsic coagulatio

156 ligonucleotides (ASOs) targeting coagulation factor XI (FXI), a member of the intrinsic coagulation p

157 ease-activated receptors (PARs), fibrinogen, factor XI (fXI), and other substrates, and a negative re

158 Since the mechanism of coagulation factor XI (FXI)-dependent thrombus growth remains unclea

159 ) and thrombin in the Apple 1 (A1) domain of factor XI (FXI).

160 ar weight kininogen (HK) in the A1 domain of factor XI (FXI).

161 hepatic mRNA encoding the hemostatic enzyme factor XI (FXI).

162 Since heparin potentiates activated factor XI (FXIa) inhibition by protease nexin-2 by provi

163 Activated Factor XI (FXIa) is a key enzyme in the amplification ph

164 I is an alternatively spliced product of the factor XI gene expressed specifically within megakaryocy

165 Previously reported mutations in the factor XI gene seem to cause deficiency primarily by red

166 presence of mutations in both alleles of the factor XI gene suggests that his bleeding disorder is ca

167 d approximately 2600 base pairs of the human factor XI gene upstream of exon one, identified transcri

168 XI is an alternative splicing product of the factor XI gene, localized to platelets and megakaryocyte

169 allikrein gene and the closely related human factor XI gene, the human KLKB1 gene contains 15 exons a

170 is considerable genetic heterogeneity in the factor XI gene.

171 We report on the genetic analysis of the factor XI genes of two African American patients: a 9-ye

172 ant FXI/G326C in which the Gly326 residue of factor XI has been mutated to Cys326, reasoning that Cys

173 The studies show that murine and human factor XI have similar structural and enzymatic properti

174 proximately 3.5 nM), whereas the recombinant factor XI heavy chain did not, demonstrating that the pl

175 ions reside in the third apple domain of the factor XI heavy chain, an area that has been shown to co

176 tor IX-binding exosites on the non-catalytic factor XI heavy chain.

177 FXI/G326C was indistinguishable from plasma factor XI in a plasma-clotting assay and in a factor IX

178 factor XI-N248 were compared with wild-type factor XI in assays for factor IX activation or platelet

179 in plasma that may help explain the role of factor XI in hemostasis and thrombosis.

180 tions, the significant amount of circulating factor XI in his plasma must be comprised entirely of ab

181 nt Apple 3 domain of factor XI and unlabeled factor XI in inhibiting [(125)I]factor XI binding to act

182 Murine factor XI differs from human factor XI in that it undergoes autoactivation slowly in

183 , Zn(2+) and Ca(2+) ions, thrombin activated factor XI in the presence of glycocalicin at rates compa

184 is without causing bleeding, but the role of factor XI in the prevention of postoperative venous thro

185 nalysis of the recombinant Apple 3 domain of factor XI indicated that amino acids R(250), K(255), F(2

186 x with prekallikrein but not in complex with factor XI, interacts with the endothelium and can mainta

187 Factor XI is a plasma glycoprotein that is required for

188 Congenital deficiency of factor XI is a rare condition associated with a mild to

189 In a purified system, murine factor XI is activated by human factor XIIa and thrombin

190 Thus, platelet factor XI is an alternative splicing product of the fact

191 Platelet factor XI is an alternatively spliced product of the fac

192 Platelet factor XI is associated with the platelet plasma membran

193 Thus, functionally active platelet factor XI is differentially expressed on platelet membra

194 Enhanced membrane exposure of platelet factor XI is independent of alpha-granule secretion, bec

195 We conclude that factor XI is localized to GPIb in membrane rafts and tha

196 of activated platelets, a preformed dimer of factor XI is not required.

197 Factor XI is the zymogen of a dimeric plasma protease, f

198 Factor XI is the zymogen of a plasma protease produced p

199 The recombination directionality factor, Xis, is a DNA bending protein that determines th

200 rypsin (Ki = 11.7 +/- 1.2 mum) and activated factor XI (Ki = 94 +/- 11 mum).

201 Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing b

202 stoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary

203 Around the time of surgery, the mean (+/-SE) factor XI levels were 0.38+/-0.01 units per milliliter i

204 se oligonucleotide that specifically reduces factor XI levels.

205 olyadenylated messenger RNA show that murine factor XI message is expressed, as expected, primarily i

206 r XI, we used mutant full-length recombinant factor XI molecules in which the platelet binding site i

207 By Northern hybridization, a factor XI mRNA transcript of approximately 1.9 kilobases

208 In situ amplification and hybridization of factor XI mRNA was positive for exon III and negative fo

209 not, indicating that, in normal hemostasis, factor XI must be activated in vivo by a protease other

210 Factor XI-N248 activates factor IX normally in a purifie

211 Iodinated factor XI-N248 binds to activated platelets with a disso

212 Activation of factor XI-N248 by thrombin in the presence of activated

213 Factor XI-N248 is the first factor XI variant described

214 Recombinant factor XI-R226 and factor XI-N248 were compared with wild-type factor XI in

215 surface of growing thrombi, such as platelet factor XI or blood-borne TF, appears essential for rapid

216 Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but

217 igh molecular weight kininogen (P<0.03), and factor XI (P<0.04) in group II vs. group III.

218 ivation by wild type factor XIa or the other factor XI/PK chimeras (0.11-0.37 microM).

219 the substitution in the third apple domain (factor XI/PKA3) had <1% of the coagulant activity of wil

220 construct is co-transfected into HeLa cells, factor XI promoter activity is enhanced approximately 10

221 The factor XI promoter functions poorly when transfected int

222 Recombinant factor XI proteins were expressed in which each of the f

223 Factor XI-R226 activates factor IX with a Michaelis-Ment

224 Recombinant factor XI-R226 and factor XI-N248 were compared with wil

225 vestigate the physiological relevance of the factor XI-raft association, the structural integrity of

226 ding to the GPIb-IX-V complex also disrupted factor XI-raft association.

227 To localize the platelet binding site on factor XI, rationally designed, conformationally constra

228 The factor XI receptor is the platelet membrane glycoprotein

229 body mass index and diabetes, only elevated factor XI remained associated with VTE risk: OR 1.8 (95%

230 that for normal (110 nmol/L TAT/min) or with factor XI replacement (119 nmol TAT/L/min).

231 minutes, which shortened to 9.7 minutes with factor XI replacement.

232 Factor XI restored the ability of thrombin to stimulate

233 prekallikrein A3 sequence was replaced with factor XI sequence to restore factor IX activation.

234 Murine factor XI shortens the clotting time of human factor XI

235 coagulant surface for binding and activating factor XI, thereby initiating the consolidation phase of

236 affinity (Kd approximately 25 nM) binding of factor XI to 947 +/- 150 sites per platelet.

237 and HK31-mer as cofactors in the binding of factor XI to activated platelets.

238 contact activation in plasma, conversion of factor XI to factor XIa proceeds through an intermediate

239 ational transition accompanies conversion of factor XI to factor XIa that conceals the Apple 3 domain

240 Optimal binding of factor XI to membrane rafts required prothrombin (and Ca

241 n (1 microm) as cofactors for the binding of factor XI to the platelet.

242 m) as a cofactor for the specific binding of factor XI to the platelet.

243 Factor XI, unlike other coagulation proteins, is a homod

244 Factor XI-N248 is the first factor XI variant described with a clear functional diff

245 ng these procoagulant factors, only elevated factor XI was a risk factor for VTE.

246 n of prekallikrein was replaced with that of factor XI was as effective as the recombinant Apple 3 do

247 The OR for factor XI was higher: 2.0 (95% CI, 1.4-2.9).

248 In contrast, messenger RNA for human factor XI was identified in liver, pancreas, and kidney.

249 We now show that factor XI was localized to lipid rafts in activated plat

250 Activation of factor XI was observed in plasma in the presence of plat

251 om its binding site on the Apple 1 domain of factor XI, we conclude that the Kringle II domain of pro

252 To localize the platelet binding site on factor XI, we used mutant full-length recombinant factor

253 (all except exon V) coding for mature plasma factor XI were amplified from human platelet mRNA.

254 ain of factor XI and inhibition by unlabeled factor XI were identical, whereas the recombinant Apple

255 The isolated recombinant Apple 3 domain of factor XI, which mediates factor XI binding to platelets

256 in with a Ki of 1.3 +/- 0.2 nm and activated factor XI with a Ki of 5.4 +/- 0.2 mum.

257 The recombinant factor XI with alanine substitutions at positions Ser(24

258 have examined the interaction of coagulation factor XI with human umbilical vein endothelial cells (H

259 binding energy mediating the interaction of factor XI with platelets is contained within the C-termi

260 Thus, the interaction of factor XI with platelets is mediated by the amino acid r

261 Ia preferentially cleaving a site on zymogen factor XI within the light chain, rather than the activa

262 relative preference of prekallikrein (PK) or factor XI/XIa (FXI/FXIa) binding to endothelial cells (H

263 factor XIa that conceals the Apple 3 domain factor XI (zymogen) platelet binding site and exposes th