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Protein Kinase A Phosphorylation of the Proteasome: A Contribution to the α‐Secretase Pathway in Human Cells
Author(s) -
Marambaud Philippe,
Wilk Sherwin,
Checler Frederic
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062616.x
Subject(s) - phosphorylation , proteasome , microbiology and biotechnology , kinase , protein kinase a , chemistry , biology , biochemistry
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.