Neurochemical Research

, Volume 36, Issue 3, pp 392–398 | Cite as

Activation of Amyloid Precursor Protein Processing by Growth Factors is Dependent on Ras GTPase Activity

  • Loredana Amigoni
  • Michela Ceriani
  • Fiorella Belotti
  • Giuseppina Minopoli
  • Enzo Martegani


The β-amyloid peptide is generated by the proteolysis of the amyloid precursor protein (APP) by the action of β- and γ-secretase. The mechanisms underlying this process are poorly understood. Using a cell-based reporter gene assay we analysed the possible signals and pathways that could be involved in APP cleavage. We used the stable cell line HeLa AG that expresses the human APP695 fused with the yeast transcription factor Gal4. This fusion protein is normally translocated into the plasma membrane and after APP-Gal4 cleavage, the AICD-Gal4 fragment released can activate the transcription of a luciferase reporter gene. Through this reporter system, we demonstrated that Ras GTPase, but not Ral and Rap, could promote APP-Gal4 cleavage. In addition HeLa AG cells stimulated with EGF or PDGF or overexpressing EGFR exhibit increased APP proteolysis in a Ras-dependent way. This process is also dependent on γ-secretase activity, being abolished by the γ-secretase inhibitor DAPT.


APP-Gal4 cleavage Ras EGF PDGF γ-secretase DAPT 


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Loredana Amigoni
    • 1
  • Michela Ceriani
    • 1
  • Fiorella Belotti
    • 1
  • Giuseppina Minopoli
    • 2
    • 3
  • Enzo Martegani
    • 1
  1. 1.Department of Biotechnology and BiosciencesUniversity of Milano-BicoccaMilanItaly
  2. 2.CEINGE Biotecnologie AvanzateNaplesItaly
  3. 3.Department of Biochemistry and Medical BiotechnologyUniversity of Napoli Federico IINaplesItaly

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