PMID- 8300647
OWN - NLM
STAT- MEDLINE
DCOM- 19940304
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 4
DP  - 1994 Jan 28
TI  - Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral 
      membrane metalloendopeptidase.
PG  - 3111-6
AB  - The beta-amyloid precursor protein (beta-APP) is a membrane spanning 
      glycoprotein. The small beta-protein domain within the precursor is presumed to 
      be the source of amyloid found in plaques characteristic of Alzheimer's disease. 
      The amino terminus of beta-APP is released from cells by cleavages that produce 
      both potentially amyloidogenic and nonamyloidogenic fragments of the carboxyl 
      terminus. We developed a cell free system that imposes specificity and 
      co-localization to characterize the proteolytic activity that cleaves the 
      precursor within the beta-protein domain. A reporter protein containing the 
      carboxyl-terminal 105 amino acids of beta-APP provided a specific substrate for 
      cleavage at Lys16 of the beta-protein. The protease inhibitor profile and 
      solubility characteristics of the activity demonstrate the cleavage is produced 
      by an integral membrane metalloendopeptidase.
FAU - Roberts, S B
AU  - Roberts SB
AD  - Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Biophysics 
      and Molecular Biology, Wallingford, Connecticut 06492.
FAU - Ripellino, J A
AU  - Ripellino JA
FAU - Ingalls, K M
AU  - Ingalls KM
FAU - Robakis, N K
AU  - Robakis NK
FAU - Felsenstein, K M
AU  - Felsenstein KM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Detergents)
RN  - 0 (Protease Inhibitors)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Alkaline Phosphatase/biosynthesis
MH  - Alzheimer Disease/metabolism
MH  - Amino Acid Sequence
MH  - Amyloid beta-Protein Precursor/biosynthesis/*metabolism
MH  - Cell Line
MH  - Cell Membrane/enzymology
MH  - Detergents/pharmacology
MH  - Enzyme Stability
MH  - Glioma
MH  - Humans
MH  - Kinetics
MH  - Lysine
MH  - Metalloendopeptidases/*metabolism
MH  - Models, Biological
MH  - Protease Inhibitors/pharmacology
MH  - *Protein Processing, Post-Translational
MH  - Substrate Specificity
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1994/01/28 00:00
MHDA- 1994/01/28 00:01
CRDT- 1994/01/28 00:00
PHST- 1994/01/28 00:00 [pubmed]
PHST- 1994/01/28 00:01 [medline]
PHST- 1994/01/28 00:00 [entrez]
AID - S0021-9258(17)42055-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Jan 28;269(4):3111-6.