Lipocortin I and lipocortin II inhibit phosphoinositide- and polyphosphoinositide-specific phospholipase C. The effect results from interaction with the substrates.
Lipocortins I and II, known to inhibit phospholipase A2, have been purified from bovine lung and tested with respect to their ability to affect the enzymatic activities of phosphoinositide- and polyphosphoinositide-specific phospholipase C from human platelets, rat liver cytosol or rat brain membranes. At 0.67 microM, both lipocortins led to complete inhibition of phospholipase C activity with either phosphatidylinositol or phosphatidylinositol 4,5-bisphosphate as substrate. The inhibition could be overcome by increasing the substrate concentration. Ultracentrifugation studies with lipocortin II showed a direct interaction between phosphatidylinositol and the lipocortin, indicating that the lipocortins inhibit phospholipase C not directly but by interacting with the substrate. In experiments with plasma membranes from [3H]inositol-labeled HL-60 cells, lipocortin II did not affect PI-specific phospholipase C activity in the absence or presence of calcium plus or minus GTP-gamma-S.
Machoczek
K
K
Abteilung Klin. Biochemie, Universität Göttingen, FRG.
Fischer
M
M
Söling
H D
HD
D000818:Animals; D017302:Annexins; D001792:Blood Platelets / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006023:Glycoproteins / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000032:analysis; D010179:Pancreas / Q000201:enzymology; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors; D054801:Phosphoinositide Phospholipase C; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010727:Phosphoric Diester Hydrolases; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017302:Annexins; D006023:Glycoproteins; D008081:Liposomes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010726:Phosphodiesterase Inhibitors; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C