Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid beta-protein precursor.
Protease nexin-II (PN-II) is a protease inhibitor that forms SDS-resistant inhibitory complexes with the epidermal growth factor (EGF)-binding protein, the gamma-subunit of nerve growth factor, and trypsin. The properties of PN-II indicate that it has a role in the regulation of certain proteases in the extracellular environment. Here we describe more of the amino-acid sequence of PN-II and its identity to the deduced sequence of the amyloid beta-protein precursor (APP). Amyloid beta-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome. A monoclonal antibody against PN-II (designated mAbP2-1) recognized PN-II in immunoblots of serum-free culture medium from human glioblastoma cells and neuroblastoma cells, as well as in homogenates of normal and Alzheimer's disease brains. In addition, mAbP2-1 stained neuritic plaques in Alzheimer's disease brain. PN-II was a potent inhibitor of chymotrypsin with an inhibition constant Ki of 6 x 10(-10)M. Together, these data demonstrate that PN-II and APP are probably the same protein. 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 proteolysis in the pathogenesis of Alzheimer's disease.
Van Nostrand
W E
WE
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Wagner
S L
SL
Suzuki
M
M
Choi
B H
BH
Farrow
J S
JS
Geddes
J W
JW
Cotman
C W
CW
Cunningham
D D
DD
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D006801:Humans; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D011480:Protease Inhibitors; D011498:Protein Precursors / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D000514:alpha 1-Antichymotrypsin / Q000235:genetics*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D011480:Protease Inhibitors; D011498:Protein Precursors; D000514:alpha 1-Antichymotrypsin; D002918:Chymotrypsin