Conventional protein kinase C (PKC)-alpha and novel PKC epsilon, but not -delta, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibroblasts.
A large soluble N-terminal fragment of Alzheimer's disease amyloid precursor protein (secreted form of APP: APPs) is produced by constitutive processing in the middle of the amyloid beta-protein portion of APP. Recent studies indicate that the activation of endogenous protein kinase C (PKC) with phorbol ester raises the rate of secretion of APPs. We constructed rat fibroblast 3Y1 cells that stably overexpress PKC isoenzymes alpha, delta, or epsilon, and analyzed the amount of APPs released from these PKC transfectants. The levels of APPs released from 3Y1 cells overexpressing PKC alpha and -epsilon were higher than those from PKC delta-transfected and control cells expressing vector only. These results suggest that specific isoforms of PKC regulate the secretion of APPs through a signaling pathway.
Kinouchi
T
T
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Sorimachi
H
H
Maruyama
K
K
Mizuno
K
K
Ohno
S
S
Ishiura
S
S
Suzuki
K
K
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D014162:Transfection
D000682:Amyloid; D007527:Isoenzymes; C512656:PRNP protein, human; D010446:Peptide Fragments; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; C496628:PRKCA protein, human; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon