Presenilin 1 mediates protein kinase C dependent alpha-secretase derived amyloid precursor protein secretion and mitogen-activated protein kinase activation in presenilin 1 transfected human embryonic kidney 293 cell.

Abstract

We investigated the role of presenilin 1 (PS1) in the secretion of alpha-secretase derived amyloid precursor protein (sAPP alpha) and associated intracellular signaling pathways. Human embryonic kidney (HEK) 293 cells were transfected with exon 9 deletion (deltaE9) mutant PS1 cDNA in an ecdyson-inducible system. sAPPalpha secretion was lower in the mutant PS1 expressing cells compared with non-expressing cells. When activated by PDBu, secretion of sAPPalpha and the level of phosphorylated mitogen activated protein kinase (MAPK) were greatly enhanced in deltaE9 PS1 uninduced cells, but not in the mutant PS1 induced cells. PD98059, a MAPK inhibitor, blocked PDBu induced sAPPalpha secretion from deltaE9 PS1 uninduced cells but had no effect on the mutant PS1 induced cells. These data indicate that PS1 mediates PDBu-induced sAPPalpha secretion and MAPK activation.