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Amyloid precursor protein processing is separately regulated by protein kinase C and tyrosine kinase in human astrocytes.

Authors
Kim, C; Jang, CH; Bang, JH; Jung, MW; Joo, I; Kim, SU; Mook-Jung, I
Citation
Neuroscience letters, 324(3):185-188, 2002
Journal Title
Neuroscience letters
ISSN
0304-39401872-7972
Abstract
Regulation of amyloid precursor protein (APP) processing by protein kinase C (PKC) and phosphotyrosine pathways was investigated in cultured human astrocytes. Phorbol 12, 13-dibutyrate (PDBu), a PKC activator, increased secretion of APPalpha 2-3-fold over control values, and GF109203X, a PKC inhibitor, blocked this effect. Similarly, platelet derived growth factor (PDGF) increased the secreted form of APPalpha (sAPPalpha) level two-fold, and genistein, a tyrosine kinase inhibitor, blocked the stimulatory effect of PDGF. Co-treatment of PDGF and PDBu resulted in a five-fold increase in the sAPPalpha production, and genistein and GF109203X did not block the stimulatory effects of PDBu and PDGF, respectively. These results indicate that both PKC and phosphotyrosine pathways are involved in APP processing in human astrocytes, but they act independently. The two pathways appear to converge to mitogen-activated protein kinase (MAPK) because PD98059, a MAPK inhibitor, blocked the effects of PDBu and PDGF on APPalpha secretion.
MeSH terms
Alzheimer Disease/*enzymology/physiopathologyAmyloid beta-Peptides/*biosynthesisAmyloid beta-Protein Precursor/*metabolismAstrocytes/drug effects/*enzymologyBrain/*enzymology/physiopathologyCells, CulturedDrug Interactions/physiologyEnzyme Inhibitors/pharmacologyFetusFlavonoids/pharmacologyGenistein/pharmacologyGlial Fibrillary Acidic Protein/metabolismHumansIndoles/pharmacologyMAP Kinase Signaling System/drug effects/physiologyMaleimides/pharmacologyPhorbol 12,13-Dibutyrate/pharmacologyPlatelet-Derived Growth Factor/pharmacologyProtein Kinase C/drug effects/*metabolismProtein-Tyrosine Kinases/drug effects/*metabolism
PMID
12009519
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
정, 민환주, 인수김, 승업묵, 인희
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