Shanghai University of Traditional Chinese Medicine, Education College of Medicine, Osaka, 530-0047, Japan; Innovative Bioinformation Research Organization, Kobe, 651-1223, Japan.
Biochem Biophys Res Commun. 2018 Dec 2;506(4):918-922. doi: 10.1016/j.bbrc.2018.10.114. Epub 2018 Nov 2.
Profilin catalyzes the exchange of actin-bound ADP to ATP. The present study investigated the role of profilin in PKCε activation. Profilin associated with PKCε in differentiated PC-12 cells under the basal conditions, which was inhibited by the PKC inhibitor GF109203X. The selective PKCε 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 PKA 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, PKCε was not activated by profilin alone. DCP-LA activated PKCε in an ATP concentration (2-500 μM)-dependent manner, and addition of profilin shifted the ATP concentration/DCP-LA-induced PKCε 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 PKCε and facilitates PKCε activation by accelerating ATP supply to PKCε.
原肌球蛋白催化肌动蛋白结合的 ADP 交换为 ATP。本研究探讨了原肌球蛋白在 PKCε 激活中的作用。在基础条件下，分化的 PC-12 细胞中原肌球蛋白与 PKCε 相关，PKC 抑制剂 GF109203X 可抑制其相关。选择性 PKCε 激活剂 DCP-LA 明显增加了这种关联，而 GF109203X 则明显阻止了这种关联。敲低原肌球蛋白可减弱 PC-12 细胞中的基础 PKC 活性，而 PKA 和 CaMKII 的基础活性不受影响。DCP-LA 将 PKC 活性增强至基础水平的约 3.5 倍，敲低原肌球蛋白可抑制该作用。在无细胞体系中，原肌球蛋白本身不能激活 PKCε。DCP-LA 以 ATP 浓度（2-500μM）依赖性方式激活 PKCε，添加原肌球蛋白会使 ATP 浓度/DCP-LA 诱导的 PKCε 活性关系曲线向左移动（向较低 ATP 浓度的方向移动）。综上所述，本研究结果表明，原肌球蛋白与激活的 PKCε 结合，并通过加速 ATP 供应来促进 PKCε 激活。
