title: The regulation of phospholipase C-gamma 1 by phosphatidic acid. Assessment of kinetic parameters.
abstract: A survey of lipids revealed that the anionic phospholipid phosphatidic acid activates both control and tyrosine-phosphorylated PLC-gamma 1. The mechanism by which phosphatidic acid activates both forms of PLC-gamma 1 was investigated using kinetic analysis. In the presence of phosphatidic acid, the substrate concentration response for control PLC-gamma 1 changes from sigmoidal to hyperbolic, while the cooperativity index decreases from 2.5 for control to 1.0 for tyrosine-phosphorylated PLC-gamma 1. The primary influence of phosphatidic acid on the control enzyme is on the cooperativity index and not the association of PLC-gamma 1 with substrate micelles, as phosphatidic acid had little effect on the micellar association constant, Ks. Phosphatidic acid also increases the activity of the tyrosine phosphorylated form of the enzyme. This increase is reflected in a decrease in the Km from 0.3- to 0.03-mol fraction phosphatidylinositol 4,5-bisphosphate. Phosphatidic acid has no effect on the Ks of the tyrosine-phosphorylated enzyme. From this data it is concluded that phosphatidic acid appears to activate PLC-gamma 1 by acting as an allosteric modifier.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0416.
authors.forename: G A
authors.initials: GA
authors.lastname: Jones
authors.forename: G
authors.initials: G
authors.lastname: Carpenter
mesh_terms: D000494:Allosteric Regulation; D002478:Cells, Cultured; D007700:Kinetics; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010766:Phosphorylation; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D010712:Phosphatidic Acids; D014443:Tyrosine; D010738:Type C Phospholipases