A G-protein signaling network mediated by an RGS protein

A wide variety of extracellular stimuli induce signal transduction through receptors coupled to heterotrimeric G proteins, which consist of , , and subunits (Gilman 1987). The G subunit has guanine nucleotide binding and GTP hydrolysis activities. Based on function and amino acid sequence homology, the G subunits can be classified into four families, including Gs, Gi/o, Gq, and G12 As exemplified by the responsiveness of our five senses to environmental stimuli, signaling mediated by trimeric G proteins is often extremely rapid and transient. A key step in achieving such a rapid response is the ability of the G subunit to switch between its GDP-and GTP-bound forms. The nucleotide binding state of G is regulated at both the GDP dissociation and GTP hydrolysis steps. Stimulation of receptors by agonists leads to a conformational change in the receptors which can function as a guanine nucleotide exchange factor to stimulate a rapid dissociation of GDP from the inactive G. The nucleotide-free G is then available to bind GTP, leading to the dissociation of G from the G heterodimer. Both the G and G subunits can interact with and regulate downstream effectors that include adenylyl cyclase, phospholipase C, and ion channels