Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency 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 approximately 50% in aged rat brain cortex, compared with that in adult and middle-aged animals. The levels of calcium-independent PKC delta and epsilon, 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 PKC delta and epsilon immunoreactivity was absent in cortex from aged animals, as well as the translocation of the calcium-dependent PKC beta, 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.
Pascale
A
A
Institute of Pharmacological Sciences, University of Milan, Italy.
Fortino
I
I
Govoni
S
S
Trabucchi
M
M
Wetsel
W C
WC
Battaini
F
F
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000032:analysis / Q000172:deficiency* / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D051381:Rats; D017208:Rats, Wistar; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000032:analysis / Q000172:deficiency* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002273:Carcinogens; D007527:Isoenzymes; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C070301:peptide I; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate