Biology of tissue factor pathway inhibitor
Recent studies of the anticoagulant activities of the tissue factor (TF) pathway inhibitor (TFPI) isoforms, TFPIa and TFPIß, have provided new insight into the biochemical and physiological meagulant activities. An alternative splicing event in the 59 untranslated region allows for translational reg...
| Main Authors: | , , , |
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| Format: | Journal Article |
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American Society of Hematology
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/45562 |
| _version_ | 1848757320243216384 |
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| author | Wood, J. Ellery, Paul Maroney, S. Mast, A. |
| author_facet | Wood, J. Ellery, Paul Maroney, S. Mast, A. |
| author_sort | Wood, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Recent studies of the anticoagulant activities of the tissue factor (TF) pathway inhibitor (TFPI) isoforms, TFPIa and TFPIß, have provided new insight into the biochemical and physiological meagulant activities. An alternative splicing event in the 59 untranslated region allows for translational regulation of TFPIß expression. TFPIa has 3 Kunitz-type inhibitor domains (K1, K2, K3) and a basic C terminus, whereas TFPIß has the K1 and K2 domains attached to a glycosylphosphatidyl inositol-anchored C terminus. TFPIa is the only isoform present in platelets, whereas endothelial cells produce both isoforms, secreting TFPIa and expressing TFPIb on the cell surface. TFPIa and TFPIß inhibit both TF-factor VIIa-dependent factor Xa (FXa) generation and free FXa. ProteinSenhances FXa inhibition by TFPIa. TFPIa produces isoform-specific inhibition of prothrombinase during the initiation of coagulation, an anticoagulant activity that requires an exosite interaction between its basic C terminus and an acidic region in the factor Va B domain. Platelet TFPIa may be optimally localized to dampen initial thrombin generation. Similarly, endothelial TFPIß may be optimally localized to inhibit processes that occur when endothelial TF is present, such as during the inflammatory response. © 2014 by The American Society of Hematology. |
| first_indexed | 2025-11-14T09:26:13Z |
| format | Journal Article |
| id | curtin-20.500.11937-45562 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:26:13Z |
| publishDate | 2014 |
| publisher | American Society of Hematology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-455622023-02-22T06:24:18Z Biology of tissue factor pathway inhibitor Wood, J. Ellery, Paul Maroney, S. Mast, A. Recent studies of the anticoagulant activities of the tissue factor (TF) pathway inhibitor (TFPI) isoforms, TFPIa and TFPIß, have provided new insight into the biochemical and physiological meagulant activities. An alternative splicing event in the 59 untranslated region allows for translational regulation of TFPIß expression. TFPIa has 3 Kunitz-type inhibitor domains (K1, K2, K3) and a basic C terminus, whereas TFPIß has the K1 and K2 domains attached to a glycosylphosphatidyl inositol-anchored C terminus. TFPIa is the only isoform present in platelets, whereas endothelial cells produce both isoforms, secreting TFPIa and expressing TFPIb on the cell surface. TFPIa and TFPIß inhibit both TF-factor VIIa-dependent factor Xa (FXa) generation and free FXa. ProteinSenhances FXa inhibition by TFPIa. TFPIa produces isoform-specific inhibition of prothrombinase during the initiation of coagulation, an anticoagulant activity that requires an exosite interaction between its basic C terminus and an acidic region in the factor Va B domain. Platelet TFPIa may be optimally localized to dampen initial thrombin generation. Similarly, endothelial TFPIß may be optimally localized to inhibit processes that occur when endothelial TF is present, such as during the inflammatory response. © 2014 by The American Society of Hematology. 2014 Journal Article http://hdl.handle.net/20.500.11937/45562 10.1182/blood-2013-11-512764 American Society of Hematology unknown |
| spellingShingle | Wood, J. Ellery, Paul Maroney, S. Mast, A. Biology of tissue factor pathway inhibitor |
| title | Biology of tissue factor pathway inhibitor |
| title_full | Biology of tissue factor pathway inhibitor |
| title_fullStr | Biology of tissue factor pathway inhibitor |
| title_full_unstemmed | Biology of tissue factor pathway inhibitor |
| title_short | Biology of tissue factor pathway inhibitor |
| title_sort | biology of tissue factor pathway inhibitor |
| url | http://hdl.handle.net/20.500.11937/45562 |