Amyloid precursor protein is not processed by furin, PACE 4, PC1/3, PC2, PC4 and PC5/6 of the furin family of proprotein processing enzymes.
Proteolytic cleavage of the amyloid precursor protein (APP) has previously been shown to release its extracellular domain into the medium. The identification of the responsible proteinase(s), termed secretase(s), is a high priority in ongoing Alzheimer research. This is hampered by the unusual characteristics of these enzyme(s) and by the fact that they cleave only membrane associated APP. We report here, using a vaccinia virus based expression system, that pig kidney PK(15) cells express full-length, membrane bound APP695, but that secretion of APP is low. This heterologous expression system allows to assay candidate secretases in a cellular context by simple co-transfection of the APP and candidate secretase cDNA containing plasmids. Eight different members of the mouse and human furin family of proprotein processing enzymes were tested in this assay, but none of them enhanced the secretion of APP. Secretion of von Willebrand's factor was used as a positive control.
De Strooper
B
B
Laboratory for Experimental Genetics, University of Leuven, Belgium.
Creemers
J W
JW
Moechars
D
D
Huylebroeck
D
D
Van De Ven
W J
WJ
Van Leuven
F
F
Van den Berghe
H
H
D000682:Amyloid / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D045683:Furin; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D008565:Membrane Proteins; D051379:Mice; D010957:Plasmids; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism*; D013381:Subtilisins / Q000378:metabolism*; D013552:Swine; D014162:Transfection; D014616:Vaccinia virus / Q000201:enzymology
D000682:Amyloid; D008565:Membrane Proteins; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors; D010450:Endopeptidases; D013381:Subtilisins; C468731:FURIN protein, human; D045683:Furin