| Abstract: | It has been demonstrated that the phospholipase C-γ (PLCγ) molecule possesses within it a phospholipase C inhibitor (PCI) region and that synthetic peptides based on the sequence of the PCI region suppress the enzymatic activity of PLC isoforms [Y. Homma and T. Takenawa (1992) J. Biol. Chem.267, 21884–218891. For the present study, the applicability of these peptides as inhibitors of PLC activity In plasma membranes was examined. Synthetic peptides, the original PCI peptide (24-mer) and a minimum octamer (YRKMRLRY), inhibit Ca2+-inducible PLC activation in digitonine-permeabilized cells, while a dodecamer sequence within the PCI region (SYYEKHALYRKM) does not. Similar results were obtained in both agonist- and GTP-binding protein-inducible PLC activation systems using purified plasma membranes. The inhibitory effect described here appears to reflect the inhibitory potency of the peptides against purified PLC isoforms. Therefore, these inhibitor peptides could provide an excellent tool for analyzing protein–protein interactions and resulting PLC activation. |
