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Regulation of Amyloid Precursor Protein Release By Protein Kinase C in Swiss 3T3 Fibroblasts a
Author(s) -
SLACK BARBARA E.,
NITSCH ROGER M.,
LIVNEH ETTA,
KUNZ GEORGE M.,
ELDAR HAGIT,
WURTMAN RICHARD J.
Publication year - 1993
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1993.tb23040.x
Subject(s) - protein kinase c , okadaic acid , phorbol , chemistry , phosphatase , amyloid precursor protein , microbiology and biotechnology , kinase , alzheimer's disease , biochemistry , medicine , enzyme , biology , disease
Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration‐dependent manner by phorbol 12‐myristate 13‐acetate. In fibroblasts overexpressing protein kinase Co (PKCα), the EC 50 for this response was 7 nM, while in control cells the EC 50 was 63 nM. The effect of PMA was inhibited by the PKC antagonist H‐7 in control cells, but not in cells that overexpressed PKCα. Basal release of APP was higher in cells that overexpressed PKCα, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKCα regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.