The soluble amyloid β precursor protein α (sAβPPα) released after α-secretase cleavage of the amyloid β precursor
protein (AβPP) has several functions including modulation of neuronal excitability and synaptic plasticity; it has
been suggested that some of these effects are mediated by activation of NF-κB via induction of PI3K/Akt signaling pathway.
We have recently described the presence of several consensus binding sites of c-Rel transcription factor in the promoter
region of the GNB2L1 gene, coding for the Receptor for Activated C Kinase -1 (RACK-1). We investigated whether
sAβPPα could influence the expression of RACK-1 through NF-κB involvement. Our data demonstrate that sAβPPα regulates
RACK-1 gene expression through PI3K/Akt-dependent pathway, inducing c-Rel nuclear translocation and NF-κB
activation. Since RACK-1 is the scaffold of protein kinase C βII (PKCβII), we turned our attention to this kinase in order
to evaluate whether sAβPPα could also influence PKCβII signalling demonstrating that sAβPPα induces PKCβII translocation
and interaction with its scaffold with consequent RACK-1/PKCβII complex increase in membrane. Altogether
these results suggest the existence of an interesting loop between the functions of the metabolic products of AβPP and the
role of PKC and that the impact of a dysregulated AβPP metabolism occurring in several conditions (from physiological
aging to injury response) may have consequences on the potential protective functions of the non amyloidogenic sAβPPα.
Keywords: sAPPα, PI3K-Akt, NF-κB, RACK-1, signal transduction, protein kinase C βII.
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