Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces.
Human blood coagulation factor XI was activated by either autoactivation or thrombin. These reactions occurred only in the presence of negatively charged materials, such as dextran sulfate (approximately Mr 500,000), sulfatide, and heparin. During the activation, factor XI was cleaved at a single Arg-Ile bond by thrombin or factor XIa to produce an amino-terminal 50-kDa heavy chain and a carboxyl-terminal 35-kDa light chain. This activation pattern is identical to that produced by factor XIIa. The addition of a small amount of thrombin and sulfatide to factor XII-deficient plasma produced shorter clotting times than when these agents were added to factor XI/factor XII combined-deficient plasma. These results suggest that the activation of factor XI by thrombin and possibly the autoactivation of factor XI proceed in plasma to lead fibrin clot formation. These reactions may have a role on an appropriate negatively charged surface in normal hemostasis.
Naito
K
K
Department of Biochemistry, University of Washington, Seattle 98195.
Fujikawa
K
K
D000838:Anions; D015153:Blotting, Western; D016264:Dextran Sulfate; D004591:Electrophoresis, Polyacrylamide Gel; D005172:Factor XI / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism*; D015945:Factor XIa / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D013917:Thrombin / Q000378:metabolism*
D000838:Anions; D007202:Indicators and Reagents; D005174:Factor XII; D005172:Factor XI; D016264:Dextran Sulfate; D015945:Factor XIa; D013917:Thrombin