-transparent.png){kind=logo}
Protease nexin-2/amyloid beta protein precursor (PN-2/A beta PP) is an abundant, secreted platelet protein which is a potent inhibitor of coagulation Factor XIa. We examined other potential anticoagulant activities of PN-2/A beta PP. Purified Kunitz protease inhibitor domain of PN-2/A beta PP and PN-2/A beta PP itself were found to prolong the coagulation time of plasma and pure Factor IXa. The Kunitz protease inhibitor domain also inhibited the ability of Factor IXa to activate Factor X. PN-2/A beta PP inhibited Factor IXa with a Ki of 7.9 to 3.9 x 10(-11) M in the absence and presence of heparin, respectively. When the second-order rate constant of PN-2/A beta PP's inhibition of Factor IXa (2.7 x 10(8) M-1min-1) was compared to that of antithrombin III (3.8 x 10(6) M-1min-1), PN-2/A beta PP was at least a 71-fold more potent inhibitor of Factor IXa than antithrombin III. PN-2/A beta PP formed a complex with Factor IXa as detected by gel filtration and ELISA. The finding that PN-2/A beta PP is a potent inhibitor of Factor IXa could help to explain the spontaneous intracerebral hemorrhages seen in patients with hereditary cerebral hemorrhage with amyloidosis Dutch-type where there is an extensive accumulation of PN-2/A beta PP in their cerebral blood vessels.
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
June 2000,
Biochemistry,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
November 1993,
The Journal of clinical investigation,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
December 2005,
Proceedings of the National Academy of Sciences of the United States of America,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
April 1995,
Thrombosis research,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
June 1990,
The Journal of biological chemistry,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
October 1995,
The Journal of biological chemistry,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
August 2000,
Thrombosis research,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
February 1991,
Biochemical and biophysical research communications,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
December 1992,
Annals of the New York Academy of Sciences,
A H Schmaier, and
L D Dahl, and
A J Rozemuller, and
R A Roos, and
S L Wagner, and
R Chung, and
W E Van Nostrand
May 1990,
Science (New York, N.Y.),
