Presenilin acts as a positive regulator of basal level activity of ERK through the Raf-MEK1 signaling pathway.
Presenilins (PS) have been reported to be functionally involved in amyloid precursor protein processing, notch receptor signaling, and programmed cell death, or apoptosis. To understand the role of PS1 in the signaling events, we investigated in this study the role of PS1 in the basal level of mitogen-activated protein kinase (MAPK) pathways using PS1(-/-) mouse embryonic fibroblast (MEF) cells from PS1-null mice. Interestingly, the basal level of ERK activity, but not JNK or p38 activity, is lower in PS1(-/-) MEF cells than in PS1(+/+) MEF cells. In PS1(-/-) MEF cells, the basal activities of Raf and MEK, the upstream signaling component of ERK, are also lower than in PS1(+/+) MEF cells. Furthermore, Elk-1 transcription activity also down-regulates in PS1(-/-) MEF cells. Collectively, our data suggest that PS can modulate the basal level of ERK activity through the Raf-MEK-dependent pathway.
Kim
Mi-Yeon
MY
Hormone Research Center, Biotechnology Research Institute, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju 500-757, Republic of Korea.
Park
Ji-Hye
JH
Choi
Eui-Ju
EJ
Park
Hee-Sae
HS
D000818:Animals; D001481:Basal Metabolism / Q000502:physiology; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053764:Presenilin-1; D015398:Signal Transduction / Q000502:physiology*; D048490:raf Kinases / Q000378:metabolism*
D008565:Membrane Proteins; D053764:Presenilin-1; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1