Phosphatidic acid modulates G protein regulation of phospholipase C-beta1 activity in membranes

Regulation of G protein stimulated phospholipase C-beta1 (PLC-beta1) activity by phosphatidic acid (PA) was determined in membranes. In cerebral cortical membranes, PLC-beta1 is under dual regulation by G protein stimulatory and inhibitory mechanisms. PA stimulated basal activity and was synergistic with G protein activation in increasing PLC-beta1 activity. Lysophosphatidic acid (LPA) also stimulated PLC-beta1 activity, but was less effective then PA. PA stimulation of PLC-beta1 activity was relatively independent of acyl chain length. PA decreased the Ca2+ dependence for G protein stimulation of PLC-beta1 activity. PA modulated the dual G protein regulation of PLC-beta1 activity, increasing stimulatory regulation and reducing inhibitory G protein regulation. The sensitivity to guanosine 5'-[gamma-thio]trisphosphate (GTP-gamma-S) and carbachol stimulation of PLC-beta1 activity was increased by PA. These results demonstrate that PA regulates both basal activity and G protein stimulation of PLC-beta1 activity. The data indicates that PA regulates the PLC-beta1 signaling pathway and thus may have an important role in the modulation of cell activation.