PLATELET COAGULATION FACTOR-XIA-INHIBITOR, A FORM OF ALZHEIMER AMYLOID PRECURSOR PROTEIN

被引：285

作者：

SMITH, RP ^{[1
]}

HIGUCHI, DA ^{[1
]}

BROZE, GJ ^{[1
]}

机构：

[1] WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT MED,DIV HEMATOL ONCOL,ST LOUIS,MO 63110

来源：

SCIENCE | 1990年 / 248卷 / 4959期

关键词：

D O I：

10.1126/science.2111585

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 β protein. It inhibits factor XIa and trypsin with a K1 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 (K1=25 ± 15 pM) in the presence of heparin.

引用

页码：1126 / 1128

页数：3

共 29 条

[1] MULTIPLE INTERMEDIATES IN THE REACTION OF BOVINE BETA-TRYPSIN WITH BOVINE PANCREATIC TRYPSIN-INHIBITOR (KUNITZ) [J].

ANTONINI, E ;

ASCENZI, P ;

MENEGATTI, E ;

GUARNERI, M .

BIOPOLYMERS, 1983, 22 (01) :363-375

[2] MONOCLONAL ANTI-HUMAN FACTOR-VII ANTIBODIES - DETECTION IN PLASMA OF 2ND PROTEIN ANTIGENICALLY AND GENETICALLY RELATED TO FACTOR-VII [J].

BROZE, GJ ;

HICKMAN, S ;

MILETICH, JP .

JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (03) :937-946

[3] ISOLATION OF THE LIPOPROTEIN ASSOCIATED COAGULATION INHIBITOR PRODUCED BY HEPG2 (HUMAN HEPATOMA) CELLS USING BOVINE FACTOR-XA AFFINITY-CHROMATOGRAPHY [J].

BROZE, GJ ;

WARREN, LA ;

GIRARD, JJ ;

MILETICH, JP .

THROMBOSIS RESEARCH, 1987, 48 (02) :253-259

[4] ISOLATION OF THE TISSUE FACTOR INHIBITOR PRODUCED BY HEPG2 HEPATOMA-CELLS [J].

BROZE, GJ ;

MILETICH, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (07) :1886-1890

[5]

CHASE T, 1970, METHOD ENZYMOL, V19, P20

[6] A NOVEL MESSENGER-RNA OF THE A4-AMYLOID PRECURSOR GENE CODING FOR A POSSIBLY SECRETED PROTEIN [J].

DESAUVAGE, F ;

OCTAVE, JN .

SCIENCE, 1989, 245 (4918) :651-653

[7] SPECTROSCOPIC DETERMINATION OF TRYPTOPHAN AND TYROSINE IN PROTEINS [J].

EDELHOCH, H .

BIOCHEMISTRY, 1967, 6 (07) :1948-&

[8]

HOOK M, 1984, ANNU REV BIOCHEM, V53, P847

[9]

ISHII SI, 1983, METHOD ENZYMOL, V91, P378

[10] PROTEIN CHEMICAL AND IMMUNOCYTOCHEMICAL STUDIES OF MENINGOVASCULAR BETA-AMYLOID PROTEIN IN ALZHEIMERS-DISEASE AND NORMAL AGING [J].

JOACHIM, CL ;

DUFFY, LK ;

MORRIS, JH ;

SELKOE, DJ .

BRAIN RESEARCH, 1988, 474 (01) :100-111

← 1 2 3 →