Enhanced generation of Alzheimer's amyloid-beta following chronic exposure to phorbol ester correlates with differential effects on alpha and epsilon isozymes of protein kinase C.

ABSTRACT: Alzheimer's amyloid precursor protein (APP) sorting and processing are modulated through signal transduction mechanisms regulated by protein phosphorylation. Notably, protein kinase C (PKC) appears to be an important component in signaling pathways that control APP metabolism. PKCs exist in at least 11 conventional and unconventional isoforms, and PKCalpha and PKCepsilon isoforms have been specifically implicated in controlling the generation of soluble APP and amyloid-beta (Abeta) fragments of APP, although identification of the PKC substrate phospho-state-sensitive effector proteins remains challenging. In the current study, we present evidence that chronic application of phorbol esters to cultured cells in serum-free medium is associated with several phenomena, namely: (i) PKCalpha down

SUBMITTER: da Cruz e Silva OA 

PROVIDER: S-EPMC2911029 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature