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.
Litosch
Irene
I
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33101, USA. ilitosch@med.miami.edu
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism / Q000494:pharmacology; D054799:Phospholipase C beta; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518035:Plcb1 protein, rat; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D002118:Calcium