The importance of the binding of factor Xa to phospholipids in the inhibitory mechanism of tissue factor pathway inhibitor: the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory action of tissue factor pathway inhibitor.
To investigate the inhibitory mechanism of tissue factor pathway inhibitor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex, which lacks its transmembrane and cytoplasmic domains. Factor VIIa-TF1-219 activity was significantly inhibited by TFPI-factor Xa complex in the presence of phospholipids, but was not in the absence of phospholipids. In addition, TFPI did not inhibit factor VIIa-TF1-219 activity in the presence of gamma-carboxyglutamic acid-domainless factor Xa. The ability of TFPI-factor Xa complex to inhibit factor VIIa-TF1-219 activity was totally dependent on the presence of phospholipids and was neutralized by prothrombin fragment 1 in a dose-dependent manner. These results indicate that the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory mechanism of TFPI and confirm that the binding of factor Xa to phospholipids through its gamma-carboxyglutamic acid domain is essential for this reaction.
Kazama
Y
Y
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, USA.
D000925:Anticoagulants / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015942:Factor VIIa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology; D011516:Prothrombin / Q000494:pharmacology
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D008074:Lipoproteins; D010446:Peptide Fragments; D010743:Phospholipids; D011498:Protein Precursors; C051928:lipoprotein-associated coagulation inhibitor; C029733:prothrombin fragment 1; D011516:Prothrombin; D015942:Factor VIIa; D015951:Factor Xa