TY - JOUR T1 - Dopamine and Ethanol Cause Translocation of ϵPKC Associated with ϵRACK: Cross-Talk between cAMP-Dependent Protein Kinase A and Protein Kinase C Signaling Pathways JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1105 LP - 1112 DO - 10.1124/mol.107.042580 VL - 73 IS - 4 AU - Lina Yao AU - Peidong Fan AU - Zhan Jiang AU - Adrienne Gordon AU - Daria Mochly-Rosen AU - Ivan Diamond Y1 - 2008/04/01 UR - http://molpharm.aspetjournals.org/content/73/4/1105.abstract N2 - We found previously that neural responses to ethanol and the dopamine D2 receptor (D2) agonist 2,10,11-trihydroxy-N-propylnorapomorphine hydrobromide (NPA) involve both ϵ protein kinase C (ϵPKC) and cAMP-dependent protein kinase A (PKA). However, little is known about the mechanism underlying ethanol- and D2-mediated activation of ϵPKC and the relationship to PKA activation. In the present study, we used a new ϵPKC antibody, 14E6, that selectively recognized active ϵPKC when not bound to its anchoring protein ϵRACK (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 ϵPKC and induced translocation of both ϵPKC and its anchoring protein, ϵRACK to a new cytosolic site. The selective ϵPKC agonist, pseudo-ϵRACK, activated ϵPKC but did not cause translocation of the ϵPKC/ϵRACK complex to the cytosol. These data suggest a step-wise activation and translocation of ϵPKC after NPA or ethanol treatment, where ϵPKC first translocates and binds to its RACK and subsequently the ϵPKC/ϵRACK complex translocates to a new subcellular site. Direct activation of PKA by adenosine-3′,5′-cyclic monophosphorothioate, Sp-isomer (Sp-cAMPS), prostaglandin E1, or the adenosine A2A receptor is sufficient to cause ϵPKC 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 ϵPKC 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. The American Society for Pharmacology and Experimental Therapeutics ER -