Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation.

Østerud, Bjarne; Rapaport, Samuel I.

doi:10.1073/pnas.74.12.5260

Cited by 738 publications

(369 citation statements)

References 18 publications

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“…[1][2][3][4][5] It has been well documented that TF serves as an initiator in some coagulation pathways via interaction with coagulation factor VII (F VII) and its activated form (F VIIa). 6,7 In many pathological processes such as atherosclerosis, septic shock, and cancers, TF is often expressed at a relatively high levels by monocytes/ macrophages and endothelial cells, thereby initiate intravascular coagulation. 8,9 In addition, TF is regarded as a member of class II cytokine receptor superfamily and may play a role other than that in coagulation.…”

Section: Introductionmentioning

confidence: 99%

Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents

et al. 1999

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The aberrant expression of tissue factor (TF) in acute promyelocytic leukemia (APL) cells has been implicated in the pathogenesis of the APL coagulopathy. In this study, we found that in APL patients receiving ATRA or As 2 O 3 treatment, the improvement in hypercoagulobility and hyperfibrinolysis paralleled the correction of plasma fibrinogen level and amelioration of bleeding symptoms. Notably, clinical improvement was also correlated to ATRA/As 2 O 3 -induced rapid decrease of membrane procoagulant activity (PCA) and TF contents of APL blasts. Consistent with the in vivo findings, the membrane PCA, TF antigen and its mRNA level within NB4 cells were rapidly down-regulated by 1 M ATRA or As 2 O 3 , while 0.2 g/ml DNR increased these TF parameters prior to its effect upon apoptosis induction. The down-regulation of TF mRNA by ATRA was partially de novo protein synthesis-dependent and at least partially attributed to a mechanism of destabilizing TF mRNA. On the other hand, in addition to its modulation on mRNA, As 2 O 3 could also induce an accelerated TF protein turnover. These distinct effects were corroborated with the properties of these agents in causing the degradation of PML-RAR␣ protein. All three therapeutic agents, however, enhanced the potential of NB4 cells to stimulate the expression of TF and PCA in endothelium. Taken together, our data suggest that the rapid and distinct regulation of TF on APL cells by these therapeutic agents might at least partially contribute to their effects on APL coagulopathy.

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Section: Introductionmentioning

confidence: 99%

Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents

et al. 1999

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“…Factors IXa and Xa then assemble, with their respective cofactors factor VIII and factor V, to generate thrombin. 1,2 Hereditary canine FVII deficiency was first described in 1962 as an incidental finding in Beagles maintained in a research colony at the Ontario Veterinary College. 3 Later, the defect was identified in Beagle research colonies in the United Kingdom 4-7 and the United States, 8 as well as in the companion Beagle population.…”

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confidence: 99%

Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog

Kaae

Callan

Brooks

2007

Veterinary Internal Medicne

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Background: Hereditary factor VII (FVII) deficiency is characterized as a mild bleeding disorder in Beagles, caused by a missense mutation in exon 5 of the FVII gene. An Alaskan Klee Kai dog with severe bleeding after trauma was diagnosed with FVII deficiency based on coagulation testing. Molecular analyses were undertaken to identify the genetic basis of the defect in this breed. Hypothesis: FVII deficiency in Alaskan Klee Kai dogs is caused by a mutation in the FVII gene. Animals: Eighteen client‐owned Alaskan Klee Kai. Methods: Coagulation screening tests and factor assays were performed to characterize the coagulopathy. All coding regions of the propositus' FVII gene were sequenced. Amplification of exon 5, sequencing, and Mnl I restriction digest experiments were performed to screen for a point mutation in the remaining 17 dogs. Results: FVII deficiency was diagnosed in 6 dogs with a median FVII activity (FVII:C) of 5% (reference range, 50–150%). All FVII‐deficient Alaskan Klee Kai were homozygous for the same mutation as FVII‐deficient Beagles (ie, a G to A transition), resulting in substitution of glycine 96 by glutamic acid. An overlap in the FVII: C values obtained from heterozygote and wild‐type dogs precluded accurate detection of carriers without genetic screening. Conclusions and Clinical Importance: FVII deficiency may be associated with a bleeding tendency and should be considered in Alaskan Klee Kai dogs with prolonged prothrombin times. Plasma FVII:C accurately identifies affected dogs, but deoxyribonucleic acid testing is required for identification of carriers.

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“…Two proteolytic cleavages are required to liberate the activation peptide from the remainder of the molecule to produce FIXa␤ (11,12). Activation may occur by two distinct mechanisms mediated by the plasma serine proteases factor VIIa (EC 3.4.21.21) and factor XIa (EC 3.4.21.27) (2,3,13,14). Activation of FIX by factor VIIa is a typical coagulation protease-substrate interaction requiring calcium, phospholipid, and a protein cofactor (the membrane protein tissue factor) (13,15).…”

mentioning

confidence: 99%

“…Activation may occur by two distinct mechanisms mediated by the plasma serine proteases factor VIIa (EC 3.4.21.21) and factor XIa (EC 3.4.21.27) (2,3,13,14). Activation of FIX by factor VIIa is a typical coagulation protease-substrate interaction requiring calcium, phospholipid, and a protein cofactor (the membrane protein tissue factor) (13,15). In this reaction the Gla domains of both FIX and factor VIIa form critical interactions with the phospholipid surface (16 -20).…”

mentioning

confidence: 99%

The Factor IX γ-Carboxyglutamic Acid (Gla) Domain Is Involved in Interactions between Factor IX and Factor XIa

Aktimur

Gabriel

Gailani

et al. 2003

Journal of Biological Chemistry

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During hemostasis, factor IX is activated to factor IXa␤ by factor VIIa and factor XIa. The glutamic acidrich ␥-carboxyglutamic acid (Gla) domain of factor IX is involved in phospholipid binding and is required for activation by factor VIIa. In contrast, activation by factor XIa is not phospholipid-dependent, raising questions about the importance of the Gla for this reaction. We examined binding of factors IX and IXa␤ to factor XIa by surface plasmon resonance. Plasma factors IX and IXa␤ bind to factor XIa with K d values of 120 ؎ 11 nM and 110 ؎ 8 nM, respectively. Recombinant factor IX bound to factor XIa with a K d of 107 nM, whereas factor IX with a factor VII Gla domain (rFIX/VII-Gla) and factor IX expressed in the presence of warfarin (rFIX-des␥) did not bind. An anti-factor IX Gla monoclonal antibody was a potent inhibitor of factor IX binding to factor XIa (K i 34 nM) and activation by factor XIa (K i 33 nM). In activated partial thromboplastin time clotting assays, the specific activities of plasma and recombinant factor IX were comparable (200 and 150 units/mg), whereas rFIX/VIIGla activity was low (<2 units/mg). In contrast, recombinant factor IXa␤ and activated rFIX/VIIa-Gla had similar activities (80 and 60% of plasma factor IXa␤), indicating that both proteases activate factor X and that the poor activity of zymogen rFIX/VII-Gla was caused by a specific defect in activation by factor XIa. The data demonstrate that factor XIa binds with comparable affinity to factors IX and IXa␤ and that the interactions are dependent on the factor IX Gla domain.

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Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation.

Cited by 738 publications

References 18 publications

Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents

Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents

Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog

The Factor IX γ-Carboxyglutamic Acid (Gla) Domain Is Involved in Interactions between Factor IX and Factor XIa

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