Negative regulation of the SAPK/JNK signaling pathway by presenilin 1

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Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid beta -protein, To understand intracellular signaling events downstream of PSI, we investigated in this study the action of PS1 on mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two functionally inactive PSI mutants, PS1(D257A) and PS1(D385A), failed to inhibit UV-stimulated SAPK/ JNK. Furthermore, H2O2- or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS+/+ mice. MEFPS1(-/-) cells were more sensitive to the H2O2-induced apoptosis than MEFPS1(+/+) cells. Ectopic expression of PS1 in MEFPS1(-/-) cells suppressed H2O2-stimulated SAPK/JNK activity and apoptotic cell death. Together, our data suggest that PS1 inhibits the stress-activated signaling by suppressing the SAPK/ JNK pathway.
Publisher
ROCKEFELLER UNIV PRESS
Issue Date
2001-04
Language
English
Article Type
Article
Keywords

FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; MAP KINASES; MISSENSE MUTATIONS; INDUCED APOPTOSIS; MAMMALIAN-CELLS; GENE; NOTCH; JNK; STRESS

Citation

JOURNAL OF CELL BIOLOGY, v.153, no.3, pp.457 - 463

ISSN
0021-9525
DOI
10.1083/jcb.153.3.457
URI
http://hdl.handle.net/10203/17520
Appears in Collection
BS-Journal Papers(저널논문)
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