DGK and nuclear signaling nuclear diacylglycerol kinases in IIC9 cells

Our investigations of DGK in IIC9 nuclei revealed the presence of two isoforms: DGK θ, which is regulated upon stimulation with the growth factor α-thrombin, and DGK δ, which is constitutively active during the investigated time course. We have previously determined that following α-thrombin stimulation, RhoA translocates to the nucleus and activates a PC-PLD1 activity. Our data indicate that RhoA inhibits nuclear DGKθ activity, suggesting that RhoA acts as a regulator to switch PA production from DGK to PC-PLD. We further suggest that the species profile of PA resulting from the two enzyme activities is likely to be different, and that there may be a topological diversity to the two pools of PA. In addition, we have identified an α-thrombin-sensitive nuclear PI-PLC activity, and have further determined that DGKθ and the PI-PLC are both localized to the nuclear lysate fraction, suggesting that DGKθ may play a role in a nuclear PI cycle. Whether the DGKθ-produced PA is a nuclear second messenger, a precursor for nuclear PI, or both, remains an open question.