Role of the G protein γ subunit in βγ complex modulation of phospholipase Cβ function

The G protein βγ complex regulates a wide range of effectors, including the phospholipase C isozymes (PLCβs). Different domains on the β subunit are known to contact phospholipase Cβ and affect its regulation. In contrast, the role of the γ subunit in Gβγ modulation of PLCβ function is not known. Results here show that the subunit C-terminal domain is involved in mediating Gβγ interactions with phospholipase Cβ. Mutations were introduced to alter the position of the post-translational prenyl modification at the C terminus of the γ subunit with reference to the β subunit. These mutants were appropriately post-translationally modified with the geranylgeranyl moiety. A deletion that shortened the C-terminal domain, insertions that extended this domain, and a point mutation, F59A, that disrupted the interaction of this domain with the β subunit were all affected in their ability to activate PLCβ to varying degrees. All mutants, however, interacted equally effectively with the G_oα subunit. The results indicate that the G protein γ subunit plays a direct role in the modulation of effector function by the βγ complex.