Protein Phosphorylation Regulates Relative Utilization of Processing Pathways for Alzheimer β/A4 Amyloid Precursor Protein

SAMUEL E. GANDY, GREGG L. CAPORASO, JOSEPH D. BUXBAUM, ODETE DA CRUZ E. SILVA, KERSTIN IVERFELDT, CHRISTER NORDSTEDT, TOSHI SUZUKI, ANDREW J. CZERNIK, ANGUS C. NAIRN, PAUL GREENGARD

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The Alzheimer amyloid precursor protein (APP) is a phosphoprotein, and the phosphorylation state of APP at Ser655 can be regulated by protein kinase C, calcium/calmodulin‐dependent protein kinase II, and okadaic acid‐sensitive protein phosphatases. Other enzymes may also play a role at Ser655 of APP and, perhaps, at other residues. Signal transduction via protein phosphorylation regulates APP metabolism. In particular, APP processing via the nonamyloidogenic secretory cleavage pathway is increased following the activation of protein kinase C or the inactivation of okadaic acid‐sensitive protein phosphatases. The mechanism(s) by which protein phosphorylation regulates APP secretory cleavage include (among others): substrate activation, substrate redistribution, protease activation and/or protease redistribution. Current experimental evidence will be discussed, addressing the relative importance of each of these possibilities and the implications for these events in the modulation of β/A4‐amyloidogenesis.

Original languageEnglish
Pages (from-to)117-121
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume695
Issue number1
DOIs
StatePublished - Sep 1993
Externally publishedYes

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