Enhancement of phospholipase D activity by overexpression of amyloid precursor protein in P19 mouse embryonic carcinoma cells.
It has been shown that phospholipase D (PLD) activity is stimulated by the beta-amyloid protein in neuronal cells. The aim of this study was to determine whether overexpression of the amyloid precursor protein (APP) affects the activity and the level of PLD expression in P19 embryonic carcinoma cells. We observed that the unstimulated basal PLD activity was higher in wild-type APP(695)-transfected cells than in non-transfected control cells. The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), has been shown to activate PLD. PMA-stimulated PLD activity was 3-fold higher in the APP overexpressing cells than in the control cells. P19 cells express two distinct PLD isozymes, PLD1 and PLD2. The level of PLD2 expression was increased by APP overexpression. Although the PKC inhibitor, GF109203X, inhibited PMA-stimulated PLD activity, it did not affect the high basal PLD activity induced by APP overexpression. Neuronal differentiation of the P19 cells by retinoic acid did not affect the basal or PMA stimulated-PLD activity. Interestingly, APP overexpression in the differentiated P19 cells also led to an increase in PLD activity. The PLD activity of the P19 cells is apparently regulated by amyloid protein through both PKC-dependent and -independent mechanisms.
Lee
M J
MJ
Department of Biochemistry, Dong-A University College of Medicine and Dong-A University Institute of Medical Science, Seo-Ku, Pusan 602-103, South Korea.
Oh
J Y
JY
Park
H T
HT
Uhlinger
D J
DJ
Kwak
J Y
JY
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000166:cytology; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010446:Peptide Fragments; C093598:amyloid beta-protein precursor 695 (681-695); D014212:Tretinoin; D011493:Protein Kinase C; C105606:phospholipase D2; D010739:Phospholipase D; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate