Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells

Erica Buoso, Fabrizio Biundo, Cristina Lanni, Stefania Aiello, Serena Grossi, Gennaro Schettini, Stefano Govoni, Marco Racchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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-kappa;B 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 βpII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCpII 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.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalCurrent Alzheimer Research
Volume10
Issue number7
DOIs
StatePublished - Nov 29 2013
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Neuronal Plasticity
Phosphatidylinositol 3-Kinases
Amyloid Precursor Protein Secretases
Amyloid
Genetic Promoter Regions
Protein Kinases
Transcription Factors
Phosphotransferases
Binding Sites
Gene Expression
Membranes
receptors for activated C kinase
Wounds and Injuries
Genes

Keywords

  • NF-κB
  • PI3K-AKt
  • Protein kinase C βII
  • RACK-1
  • sAPPα
  • Signal transduction

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells. / Buoso, Erica; Biundo, Fabrizio; Lanni, Cristina; Aiello, Stefania; Grossi, Serena; Schettini, Gennaro; Govoni, Stefano; Racchi, Marco.

In: Current Alzheimer Research, Vol. 10, No. 7, 29.11.2013, p. 697-705.

Research output: Contribution to journalArticle

Buoso, E, Biundo, F, Lanni, C, Aiello, S, Grossi, S, Schettini, G, Govoni, S & Racchi, M 2013, 'Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells', Current Alzheimer Research, vol. 10, no. 7, pp. 697-705. https://doi.org/10.2174/15672050113109990145
Buoso, Erica ; Biundo, Fabrizio ; Lanni, Cristina ; Aiello, Stefania ; Grossi, Serena ; Schettini, Gennaro ; Govoni, Stefano ; Racchi, Marco. / Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells. In: Current Alzheimer Research. 2013 ; Vol. 10, No. 7. pp. 697-705.
@article{ce3b34da028b4302a40aedac684408e3,
title = "Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells",
abstract = "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-kappa;B 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 βpII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCpII 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 = "NF-κB, PI3K-AKt, Protein kinase C βII, RACK-1, sAPPα, Signal transduction",
author = "Erica Buoso and Fabrizio Biundo and Cristina Lanni and Stefania Aiello and Serena Grossi and Gennaro Schettini and Stefano Govoni and Marco Racchi",
year = "2013",
month = "11",
day = "29",
doi = "10.2174/15672050113109990145",
language = "English (US)",
volume = "10",
pages = "697--705",
journal = "Current Alzheimer Research",
issn = "1567-2050",
publisher = "Bentham Science Publishers B.V.",
number = "7",

}

TY - JOUR

T1 - Modulation of Rack-1/PKCβII signalling by soluble AβPPα in SH-SY5Y cells

AU - Buoso, Erica

AU - Biundo, Fabrizio

AU - Lanni, Cristina

AU - Aiello, Stefania

AU - Grossi, Serena

AU - Schettini, Gennaro

AU - Govoni, Stefano

AU - Racchi, Marco

PY - 2013/11/29

Y1 - 2013/11/29

N2 - 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-kappa;B 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 βpII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCpII 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.

AB - 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-kappa;B 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 βpII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCpII 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.

KW - NF-κB

KW - PI3K-AKt

KW - Protein kinase C βII

KW - RACK-1

KW - sAPPα

KW - Signal transduction

UR - http://www.scopus.com/inward/record.url?scp=84888244424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888244424&partnerID=8YFLogxK

U2 - 10.2174/15672050113109990145

DO - 10.2174/15672050113109990145

M3 - Article

VL - 10

SP - 697

EP - 705

JO - Current Alzheimer Research

JF - Current Alzheimer Research

SN - 1567-2050

IS - 7

ER -