Gelatinase A possesses a beta-secretase-like activity in cleaving the amyloid protein precursor of Alzheimer's disease.
The ability of the 72 kDa gelatinase A to cleave the amyloid protein precursor (APP) was investigated. HeLa cells were transfected with an APP695 plasmid. The cells were incubated with gelatinase A, which cleaved the 110 kDa cell-surface APP, releasing a 100 kDa form of the protein. A peptide homologous to the beta-secretase site was cleaved by gelatinase A adjacent to a glutamate residue at position -3 (beta A4 numbering system). A peptide homologous to the alpha-secretase site was not cleaved. The results demonstrate that 72 kDa gelatinase A is not an alpha-secretase, but that it may have a beta-secretase activity.
Laboratory of Molecular Neurobiology, University of Melbourne, Parkville, Vic., Australia.
R N
RN
LePage
A J
AJ
Fosang
S J
SJ
Fuller
G
G
Murphy
G
G
Evin
K
K
Beyreuther
C L
CL
Masters
D H
DH
Small
D053674:Aggrecans; D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D010450:Endopeptidases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D018093:Gelatinases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D037181:Lectins, C-Type; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D053674:Aggrecans; D016564:Amyloid beta-Protein Precursor; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2