Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein.

@article{Smith1990PlateletCF,
  title={Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein.},
  author={R P Smith and Darryl A. Higuchi and George J. Broze},
  journal={Science},
  year={1990},
  volume={248 4959},
  pages={
          1126-8
        }
}
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… 
Characterization of platelet-releasable forms of beta-amyloid precursor proteins: the effect of thrombin.
TLDR
Two carboxy-terminal truncated forms of the beta APP, beta APP-751 andbeta APP-770, are shown to be the predominant isoforms secreted by platelets, responsible for the higher concentration of beta APP in serum compared with plasma, and thrombin dose-response data show that release of Beta APP is most consistent with alpha granule localization within the platelet.
Protease nexin-2/amyloid beta protein precursor. A tight-binding inhibitor of coagulation factor IXa.
TLDR
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.
“New” Coagulation Inhibitors
TLDR
Blood coagulation proceeds through a series of reactions in which plasma zymogens of serine proteases are sequentially activated by limited proteolytic cleavage by the Kunitz family of protease inhibitors.
Coagulation Factor XIa Cleaves the RHDS Sequence and Abolishes the Cell Adhesive Properties of the Amyloid β-Protein (*)
TLDR
It is shown thatFXIa can proteolytically alter Aβ and therefore possibly modify its physiological and perhaps pathological properties and a new potential biological function for FXIa in the modulation of cell adhesion is suggested.
Potential Role of Protease Nexin‐2/Amyloid β‐Protein Precursor as a Cerebral Anticoagulant a
TLDR
The findings suggest that PN-2/APP may play a role in the regulation of blood coagulation and platelets may serve as a systemic vehicle to deliver large amounts of this protein to sites of vascular injury.
Platelet protease nexin-2/amyloid beta-protein precursor. Possible pathologic and physiologic functions.
TLDR
Findings indicate that PN-2/APP regulates blood coagulation, and possibly other proteolytic events, at sites of vascular injury.
Enhanced Plasmin Inhibition by a Reactive Center Lysine Mutant of the Kunitz-type Protease Inhibitor Domain of the Amyloid β-Protein Precursor (*)
TLDR
It is suggested that the KPI-Lys domain has enhanced anti-fibrinolytic and diminished factor XIa inhibitory properties compared to the native KPI domain of AβPP.
Secreted Forms of the Amyloid-β Precursor Protein Are Ligands for the Class A Scavenger Receptor*
TLDR
The results suggest that the SR-A contributes to the clearance of sAPP and that sAPP competes for the cell association of otherSR-A ligands.
...
...

References

SHOWING 1-10 OF 26 REFERENCES
Regulation of factor XIa activity by platelets and alpha 1-protease inhibitor.
TLDR
The hypothesis that platelets can regulatefactor XIa-catalyzed Factor IX activation by secreting an inhibitor of Factor XIa that may act primarily outside the platelet microenvironment and by protecting Factor XI a from inhibition is supported.
Protease nexin-II, a potent anti-chymotrypsin, shows identity to amyloid β-protein precursor
TLDR
The regulation of extracellular proteolysis by PN-II and the deposition of at least parts of the molecule in senile plaques is consistent with previous reports that implicate altered proteolytic activity in the pathogenesis of Alzheimer's disease.
The effect of platelets in the activation of human blood coagulation factor IX by factor XIa
TLDR
Activated human platelets inhibited factor IX activation by factor XIa in a dose- dependent manner, whereas unstimulated platelets had no effect, and data suggest that platelets release an antiprotease offactor XIa that reversibly inhibits factor XIA.
Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity
TLDR
It is suggested that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism, and a cDNA library of a human glioblastoma cell line is isolated, together with a new cDNA which contains a 225-nucleotide insert.
The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II
TLDR
The deduced amino-terminal sequence of APP is iden-tical to the sequence of a cell-secreted protease inhibitor, protease nexin-II (PN-II)8, and it is concluded that the secreted form of APP with the Kunitz protease inhibitors domain is PN-II.
A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors
TLDR
The sequence of a closely related amyloid cDNA, A4751, is distinguished from A4695 by the presence of a 168 base-pair sequence which adds 57 amino acids to, and removes one residue from, the predicted A4 695protein.
Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells.
  • G. BrozeJ. Miletich
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1987
TLDR
A TFI secreted by HepG2 cells (human hepatoma cell line) was isolated from serum-free conditioned medium in a four-step procedure including CdCl2 precipitation, diisopropylphosphoryl-factor Xa affinity chromatography, Sephadex G-75 superfine gel filtration, and Mono Q ion-exchange chromatography.
...
...