Protein kinase A phosphorylation of the proteasome: A contribution to the α-secretase pathway in human cells

Philippe Marambaud, Sherwin Wilk, Frederic Checler

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The β-amyloid precursor protein undergoes a physiological cleavage by α-secretase that leads to the release of a secreted C-terminally truncated fragment called APPα and likely concomitantly reduces the formation of the amyloidogenic Aβ peptide. Here we demonstrate that APPα secretion is increased by the protein kinase A (PKA) effectors 8-bromo cyclic AMP and forskolin in human embryonic kidney cells (HK293), and that this can be prevented by a proteasome inhibitor. Furthermore, we establish that PKA effectors but not protein kinase C agonists increase the chymotrypsin-like activity and phosphorylation state of the proteasome in vitro and in vivo in HK293 cells. Altogether, this report demonstrates that the α-secretase pathway is under the control of PKA in human cells and that the proteasome likely contributes, either directly or through yet unknown intermediates, to the PKA-stimulated APPα secretion in human cells.

Original languageEnglish
Pages (from-to)2616-2619
Number of pages4
JournalJournal of Neurochemistry
Volume67
Issue number6
DOIs
StatePublished - Dec 1996

Keywords

  • Alzheimer's disease
  • HK293 cells
  • Proteasome
  • Protein kinase A
  • α-Secretase
  • β-Amyloid precursor protein APPα fragment

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