FUNCTIONAL IMPAIRMENT IN PROTEIN KINASE C BY RACK1 (Receptor for Activated C Kinase 1) DEFICENCY IN AGED RAT BRAIN CORTEX

Several laboratories have reported a lack of
protein kinase C (PKC) activation in response to various
stimuli in the brain of aged rats . It has been suggested
that changes in lipid membrane composition could be
related to this functional deficit. However, recent evidence
has indicated that the translocation of PKC to the
different subcellular compartments is controlled by protein-
protein interactions . Recently, a class of proteins,
termed receptors for activated C kinase (RACKS), have
been described that bind PKC. The present study was
conducted to determine whether alterations in RACK1,
the best-characterized member of RACKS, were associated
with changes in translocation and expression of
PKC. Quantitative immunoblotting revealed that RACK1
content was decreased by -50% in aged rat brain cortex,
compared with that in adult and middle-aged animals.
The levels of calcium-independent PKC6 and E, interacting
with RACK1, and related calcium-independent
PKC activity were not modified by the aging process.
By comparison, phorbol ester-stimulated translocation of
this activity and of PKC6 and e immunoreactivity was
absent in cortex from aged animals, as well as the translocation
of the calcium-dependent PKCß, also known to
interact with RACK1 . These results indicate that a deficit
in RACK1 may contribute to the functional impairment in
PKC activation observed in aged rat brain.