title: Inhibitory spectra of purified protease nexin-II and related proteins towards cellular proteinases.
abstract: Amyloid beta protein (beta/A4) is deposited in senile plaques of patients with Alzheimer's disease. This protein is derived from a larger membrane-associated protein, termed amyloid precursor protein (APP). The constitutive processing of APP occurs at the central portion of beta/A4, resulting in the release of large N-terminal peptides. We have purified these peptides from the culture medium of cDNA-transfected COS-1 cells. Some of the isoforms contain the Kunitz-type protease inhibitor (KPI) domain and strongly inhibit trypsin, chymotrypsin and plasmin, but do not inhibit kallikrein, prolyl endopeptidase or granzyme A. The peptides also do not inhibit cysteine proteases such as cathepsin B or calpain. Soluble APPs lacking the KPI domain fail to inhibit any of these proteases. The results indicate that the KPI domain in soluble APPs has protease inhibitory activity against certain serine proteases.
authors.affiliation: National Institute of Neuroscience, Kodaira, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimokawa
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: K
authors.initials: K
authors.lastname: Tagawa
authors.forename: T
authors.initials: T
authors.lastname: Miyatake
authors.forename: H
authors.initials: H
authors.lastname: Sugita
authors.forename: S
authors.initials: S
authors.lastname: Ishiura
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D018076:DNA, Complementary; D004586:Electrophoresis; D006801:Humans; D008969:Molecular Sequence Data; D015849:Plasminogen Inactivators / Q000737:chemistry / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D012995:Solubility; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D015849:Plasminogen Inactivators; D015842:Serine Proteinase Inhibitors