Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein.
An inhibitor of coagulation factor XIa was purified from serum-free conditioned medium of HepG2 liver cells. Platelets stimulated with thrombin or calcium ionophore (A23187) secrete a protein functionally and immunologically identical to the inhibitor, implying a role for this inhibitor in hemostasis. Analysis of the amino-terminal amino acid sequence and immunologic reactivity showed the inhibitor to be a truncated form of the Alzheimer's amyloid precursor protein that contains a Kunitz-type serine protease inhibitor domain and at least a portion of the amyloid beta protein. It inhibits factor XIa and trypsin with a Ki of 450 +/- 50 pM and 20 +/- 10 pM, respectively. Heparin (1 unit/ml) did not significantly effect inhibition of trypsin, but inhibition of XIa was 15 times greater (Ki = 25 +/- 15 pM) in the presence of heparin.
Smith
R P
RP
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.
Higuchi
D A
DA
Broze
G J
GJ
D000595:Amino Acid Sequence; D000682:Amyloid / Q000276:immunology; D016564:Amyloid beta-Protein Precursor; D001792:Blood Platelets / Q000032:analysis*; D001798:Blood Proteins / Q000276:immunology / Q000302:isolation & purification* / Q000502:physiology; D003429:Cross Reactions; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000302:isolation & purification*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D001798:Blood Proteins; D011498:Protein Precursors; D015842:Serine Proteinase Inhibitors; D015945:Factor XIa