Activation of protein kinase C increases the extracellular release of the transmembrane amyloid protein precursor of Alzheimer's disease.
The beta A4 peptide is the major constituent of the amyloid core of abundant senile plaques found in the cerebral cortex of patients with Alzheimer's disease. This amyloid peptide is synthesized as part of a large transmembrane amyloid protein precursor or APP. In addition to the highly expressed transmembrane APP isoforms, an mRNA encoding a secreted APP lacking the transmembrane domain has been identified. A cleavage of the transmembrane protein also yields an extracellular soluble APP fragment. The effect of phorbol esters on the release of the extracellular APP was studied in transfected Chinese hamster ovary cells which stably express either a transmembrane or a secreted APP isoform. The activation of protein kinase C by phorbol-12,13-dibutyrate increased the extracellular release of the transmembrane APP resulting from its proteolytic cleavage, while 4-beta-phorbol, which does not activate protein kinase C, did not significantly affect the recovery of the soluble APP. On the contrary, the recovery of APP secreted in the culture medium without proteolytic cleavage was not increased by protein kinase C-mediated phosphorylation.
Demaerschalck
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Université Catholique de Louvain, Laboratoire de Neurochimie, Brussels, Belgium.
Delvaux
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Octave
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D000470:Alkaloids / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000201:enzymology; D006224:Cricetinae; D003412:Cricetulus; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D014162:Transfection
D000470:Alkaloids; D016564:Amyloid beta-Protein Precursor; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D019311:Staurosporine