Secretory processing of the Alzheimer amyloid β A4 protein precursor is increased by protein phosphorylation

Susan L. Gillespie, Todd E. Golde, Steven G. Younkin

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


The 39-43 residue polypeptide (amyloid β protein, βA4) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursors referred to as the amyloid βA4 protein precursor (βAPP). In each of the 695, 751, and 770 residue precursors, the 43 residue βA4 is an internal peptide that begins 99 residues from the COOH-terminus of the βAPP. Each holoform is normally cleaved within the βA4 to produce a large secreted derivative as well as a small membrane associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire βA4 peptide. In this study, we employ cells stably transfected with full length βAPP695, βAPP751, or βAPP770 expression constructs to show that phorbol ester activation of protein kinase C substantially increases the production of secreted forms from each isoform. By increasing processing of βAPP in the secretory pathway, PKC phosphorylation may help to prevent amyloid deposition.

Original languageEnglish (US)
Pages (from-to)1285-1290
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Sep 30 1992

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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