Dopamine and Ethanol Cause Translocation of 
PKC Associated with RACK: Cross-talk Between PKA and PKC Signaling PathwaysMolecular Pharmacology Fast Forward
First published on January 17, 2008;
Previously we found that neural responses to ethanol and the dopamine D2 receptor (D2) agonist NPA involve both epsilon protein kinase C (
PKC) and cAMP-dependent protein kinase A (PKA). However, little is known about the mechanism underlying ethanol- and D2-mediated activation of PKC and the relationship to PKA activation. In the present study, we used a new
PKC antibody, 14E6, that selectively recognizes active PKC when not bound to its anchoring protein RACK (receptor for activated C-kinase), and PKC isozyme-selective inhibitors and activators, to measure PKC translocation and catalytic activity.We show here that ethanol and NPA activated
PKC and also induced translocation of both PKC and its anchoring protein, RACK to a new cytosolic site. The selective PKC agonist, pseudo-RACK, activated PKC but did not cause translocation of the PKC/RACK complex to the cytosol.These data suggest a step-wise activation and translocation of
PKC following NPA or ethanol treatment where PKC first translocates and binds to its RACK and subsequently the PKC/RACK complex translocates to a new subcellular site. Direct activation of PKA by Sp-cAMPS, PGE1 or the adenosine A2A receptor is sufficient to cause PKC translocation to the cytosolic compartment in a process that is dependent on PLC activation and requires PKA activity.These data demonstrate a novel cross-talk mechanism between
PKC and PKA signaling systems. PKA and PKC signaling have been implicated in alcohol rewarding properties in the mesolimbic dopamine system.Cross-talk between PKA and PKC may underlie some of the behaviors associated with alcoholism.
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