RGS domains bind directly to activated Ga subunits and act as GTPase-activating proteins (GAPs) to attenuate and/or modulate hormone and neurotransmitter receptor-initiated signaling by both Ga-GTP and Gbg. RGS proteins shorten the lifetime of the activated G protein. Western blot analysis shows strong expression of RGS14 as a primarily cytosolic protein restricted to brain and spleen. It is suggested that RGS14 may constitute a bridging molecule that allows cross-regulation of signaling pathways downstream from G protein-coupled receptors.