Premium
P3–408: Presenilin–1 interacts with RIP1 kinase and participates in cytokine mediated NF–κB activation
Author(s) -
Harte Frances M.,
McCarthy Justin V.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1679
Subject(s) - presenilin , biology , immunoprecipitation , iκb kinase , microbiology and biotechnology , kinase , signal transduction , hek 293 cells , nf κb , receptor , alzheimer's disease , genetics , cell culture , medicine , disease
PS2 for regulating PLC signalling. Methods: To evaluate the dependence of PLC on PSs we measured PLC activity (as the hydrolysis of phosphoinositides), Protein kinase C (PKC) activation in mouse embryonic fibroblast (MEF) cells lacking PS1, PS2, or both. Results: PLC activity, and activation of the calcium-dependent PKC isoforms, PKC and PKC were lower in PS1 and PS2 double knockout MEFs after 2,4,6-trimethylN-(m/o-3-trifluoromethylphenyl) benzenesulfonamide; oxotremorine-M (3M3FBS) stimulation of PLC. Protein levels of PKC and PKC were significantly lower in PS1 and PS2 double knockout MEFs, as compared to the other cell types. In contrast, levels of the calcium-independent PKC isoform were significantly elevated in PS1 and PS2 double knockout as well as in PS1 knockout fibroblasts. Since ER calcium signalling can be regulated through APP dependent gene transcription, we investigated whether similar mechanisms regulate the levels of PKC isoforms. Using APP knockout MEFs and siRNA silencing of APP expression in HEK cells we showed that PKC expression is regulated in an APP dependent manner. Pharmacological inhibition of -secretase with L-685,458 did not affect protein levels of the different PKC isoforms. Conclusion: Together, our results show a PS dependence for the activation of PLC and PKC as well as for levels of different PKC isoforms. Levels of PKC were dependent on the presence of PS1 but not PS2. Furthermore, PKC levels may be APP dependent but -secretase independent.