PMID- 1696210
OWN - NLM
STAT- MEDLINE
DCOM- 19900911
LR  - 20190620
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 267
IP  - 2
DP  - 1990 Jul 16
TI  - Does the Kunitz domain from the Alzheimer's amyloid beta protein precursor 
      inhibit a kallikrein responsible for post-translational processing of nerve 
      growth factor precursor?
PG  - 207-12
AB  - Alternative splicing of the Alzheimer's amyloid beta protein precursor (ABPP) 
      message leads to the production of several variants of this precursor 
      polypeptide. Two of these variants contain a domain that is highly homologous to 
      members of the Kunitz class of protease inhibitors. In order to initiate a study 
      of the physiological role of this domain, we have produced active ABPP Kunitz 
      inhibitor by constructing and expressing a synthetic gene in E. coli. Nerve 
      growth factor (NGF) deficiency has been suggested as a possible cause of the 
      neural degeneration characteristic of Alzheimer's disease, and trypsin and 
      gamma-NGF are the two enzymes that have been shown to be capable of processing 
      beta-NGF precursor to active, mature beta-NGF in vitro, therefore, the 
      specificity of purified recombinant ABPP Kunitz inhibitor was analyzed with 
      respect to these two proteases. Binding of isolated ABPP Kunitz domain both to 
      trypsin (Ki,app less than 10 nM and to gamma-NGF (Ki,app = 300 nM) was observed. 
      This difference in binding to the two proteases correlates with the approximately 
      20-fold higher rate observed for in vitro processing of the beta-NGF precursor by 
      trypsin compared to processing by gamma-NGF, indicating that perhaps the 
      inhibitor mimics the interaction of the beta-NGF precursor with proteases. The 
      kallikrein actually responsible for beta-NGF precursor processing in vivo is 
      unknown, but these results suggest that it is capable of being significantly 
      inhibited by exposure to the ABPP Kunitz domain.
FAU - Castro, M
AU  - Castro M
AD  - Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854.
FAU - Marks, C B
AU  - Marks CB
FAU - Nilsson, B
AU  - Nilsson B
FAU - Anderson, S
AU  - Anderson S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Amyloid)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protein Precursors)
RN  - 0 (Recombinant Proteins)
RN  - 9087-70-1 (Aprotinin)
RN  - EC 3.4.21.- (Kallikreins)
SB  - IM
MH  - Alzheimer Disease/*genetics/metabolism
MH  - Amino Acid Sequence
MH  - Amyloid/biosynthesis/*physiology
MH  - Amyloid beta-Protein Precursor
MH  - Aprotinin/biosynthesis/*physiology
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - Escherichia coli/metabolism
MH  - Gene Expression Regulation
MH  - Genetic Vectors
MH  - Humans
MH  - Kallikreins/*antagonists & inhibitors
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/*metabolism
MH  - Protein Precursors/biosynthesis/*physiology
MH  - *Protein Processing, Post-Translational
MH  - Recombinant Proteins/physiology
EDAT- 1990/07/16 00:00
MHDA- 1990/07/16 00:01
CRDT- 1990/07/16 00:00
PHST- 1990/07/16 00:00 [pubmed]
PHST- 1990/07/16 00:01 [medline]
PHST- 1990/07/16 00:00 [entrez]
AID - 0014-5793(90)80926-A [pii]
AID - 10.1016/0014-5793(90)80926-a [doi]
PST - ppublish
SO  - FEBS Lett. 1990 Jul 16;267(2):207-12. doi: 10.1016/0014-5793(90)80926-a.