Profilin catalyzes the exchange of actin-bound ADP to ATP. The present study investigated the role of profilin in PKC epsilon activation. Profilin associated with PKC epsilon in differentiated PC-12 cells under the basal conditions, which was inhibited by the PKC inhibitor GF109203X. The selective PKC epsilon activator DCP-LA markedly increased the association, which was clearly prevented by GF109203X. The basal PKC activity in PC-12 cells was attenuated by knocking-down profilin, while the basal activities of PICA and CaMKII were not affected. DCP-LA enhanced the PKC activity to approximately 3.5 folds of the basal levels, and the effect was suppressed by knocking-down profilin. In the cell-free system, PKC epsilon was not activated by profilin alone. DCP-LA activated PKC epsilon in an ATP concentration (2-500 mu M)-dependent manner, and addition of profilin shifted the ATP concentration/DCP-LA-induced PKC epsilon activity relation curve to the left (the direction of lower ATP concentrations). Taken together, the results of the present study indicate that profilin binds to activated PKC epsilon and facilitates PKC epsilon activation by accelerating ATP supply to PKC epsilon. (C) 2018 Elsevier Inc. All rights reserved.