Activation of polyphosphoinositide phospholipase C by fluoride in WRK1 cell membranes

Abstract

Partially purified plasma membranes prepared from myo-[³H]inositol-prelabeled WRK1 cells exhibit a phosphatidylinositol 4,5-bisphosphate (PIP₂) phospholipase C activity sensitive to NaF. NaF increased the production of IP₂ and IP₃ in a time- and concentration-dependent manner. The maximal increase in IP₂ and IP₃ production rates represented 400 ± 18 and 360 ± 40% of the basal production rate, respectively. Half-maximum stimulation was reached with 2–4 mM NaF. The observed effect was specific for F⁻. Aluminium potentiated fluoride-induced IP₃ and IP₂, accumulation in a concentration-dependent manner. The effect of fluoride on the PIP₂ phospholipase C from WRK1 cell membranes appears to be similar to the well-documented effect of F⁻ on the well-characterized N_s. N_i and transducin GTP-binding proteins. This observation constitutes an additional argument to suggest that a GTP-binding protein is involved in the process of receptor-mediated activation of PIP₂ phospholipase C.