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

Raymond P. Smith, Darryl A. Higuchi, George J. Broze

Research output: Contribution to journalArticlepeer-review

253 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1126-1128
Number of pages3
JournalScience
Volume248
Issue number4959
DOIs
StatePublished - 1990

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