Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder.
BACKGROUND
Membrane protein kinase C (PKC) activity is increased in frontal cortex of subjects with bipolar affective disorder, and lithium was demonstrated to inhibit PKC translocation to membranes. Protein kinase C is anchored to the membrane via the receptor for activated C kinase-1 (RACK1), suggesting that interactions between these proteins may be altered in bipolar disease.


METHODS
The levels of RACK1 coimmunoprecipitating with PKC isozymes were compared in homogenates of frontal cortex slices from postmortem bipolar subjects and matched control subjects.


RESULTS
Receptor for activated C kinase-1 was located exclusively in membranes and, in control brains, the levels of RACK1 that coimmunoprecipitated with most PKC isozymes were increased by stimulation with the PKC activator, phorbol 12-myristate, 13-acetate (PMA). The association of RACK1 with membrane gammaPKC and zetaPKC was increased under basal conditions in bipolar relative to control brains. Stimulation with PMA increased the amount of RACK1 that coimmunoprecipitated with the alpha, beta, gamma, delta, and varepsilonPKC isozymes, but not zetaPKC, in bipolar tissues over that elicited in control tissues.


CONCLUSIONS
These data suggest that the increased association of RACK1 with PKC isozymes may be responsible for the increases in membrane PKC and in its activation that were previously observed in frontal cortex of bipolar affective disorder brains.
Wang
H
H
Laboratory of Molecular Pharmacology, MCP Hahnemann School of Medicine, 245 N. 15th Street, Philadelphia, PA 19102, USA.
Friedman
E
E
D000368:Aged; D001714:Bipolar Disorder / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D012016:Reference Values; D014178:Translocation, Genetic / Q000502:physiology
D007527:Isoenzymes; D010455:Peptides; D000075370:Receptors for Activated C Kinase; C070301:peptide I; D011493:Protein Kinase C