This chapter describes events that transpired in the mid-1990s during the pioneering days of RGS protein research. This period began with early studies of Sst2 in yeast, EGL-10 in nematodes, and the discovery of an expansive family of similar proteins in animals. Within a period of only 2 years, the RGS gene family was first identified, functionally characterized in diverse organisms, and their mechanism of action firmly established. Long considered a three-component signaling system (comprised of a receptor, G protein, and effector enzyme), the discovery of RGS proteins revealed a critical new component of the signaling apparatus, and resolved a long-recognized discrepancy in the rates of G protein inactivation measured in vitro and in vivo.
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