Interaction of GTP‐binding proteins with calmodulin

Two GTP‐binding proteins (G i and G o ), which were the substrates for islet‐activating protein, pertussis toxin, were purified from bovine cerebral cortical membranes. Both G i and G o completely inhibited calmodulin‐stimulated cyclic nucleotide phosphodiesterase activity. The same concentrations of these proteins, however, had no appreciable effect on the basal phosphodiesterase activity. The isolated G i α and βγ subunits of GTP‐binding proteins were potent inhibitors of the calmodulin‐stimulated phosphodiesterase activity, but G o α was very weak. Therefore, the βγ subunits were likely to be the major active molecules in the brain membranes. GTP‐binding proteins were shown to bind directly to calmodulin in a Ca 2+ ‐dependent manner by a gel permeation binding experiment.