Presenilin dependence of phospholipase C and protein kinase C signaling

Nodi Dehvari, Angel Cedazo-Minguez, Ola Isacsson, Tatjana Nilsson, Bengt Winblad, Helena Karlström, Eirikur Benedikz, Richard F Cowburn

Research output: Contribution to journalJournal articleResearchpeer-review


Presenilins (PSs) are involved in processing several proteins such as the amyloid precursor protein (APP), as well as in pathways for cell death and survival. We previously showed that some familial Alzheimer's disease PS mutations cause increased basal and acetylcholine muscarinic receptor-stimulated phospholipase C (PLC) activity which was gamma-secretase dependent. To further evaluate the dependence of PLC on PSs we measured PLC activity and the activation of variant protein kinase C (PKC) isoforms in mouse embryonic fibroblasts (MEFs) lacking either PS1, PS2, or both. PLC activity and PKCalpha and PKCgamma activations were significantly lower in PS1 and PS2 double knockout MEFs after PLC stimulation. Protein levels of PKCalpha and PKCgamma were lower in PS1 and PS2 double knockout MEFs. In contrast, PKCdelta levels were significantly elevated in PS1 and PS2 double knockout as well as in PS1 knockout MEFs. Also, PKCdelta levels were lowered after transfection of PS1 into PS1 knockout or PS double knockout MEFs. Using APP knockout MEFs we showed that the expression of PKCalpha, but not the other PKC isoforms is partially dependent on APP and can be regulated by APP intracellular domain (AICD). These results show that PLC and PKC activations are modulated by PS and also that PSs differentially regulate the expression of PKC isoforms by both APP/AICD-dependent and independent mechanisms.

Original languageEnglish
JournalJournal of Neurochemistry
Issue number3
Pages (from-to)848-57
Number of pages10
Publication statusPublished - Aug 2007
Externally publishedYes


  • Alzheimer Disease
  • Amyloid beta-Protein Precursor
  • Animals
  • Brain
  • Cells, Cultured
  • Down-Regulation
  • Fibroblasts
  • Gene Expression Regulation, Enzymologic
  • Isoenzymes
  • Journal Article
  • Mice
  • Mice, Knockout
  • Presenilin-1
  • Presenilin-2
  • Presenilins
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Protein Kinase C-delta
  • Research Support, Non-U.S. Gov't
  • Signal Transduction
  • Transfection
  • Type C Phospholipases

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