Mechanisms Involved in G-protein Activation by Hormone Receptors

Abstract

Signal-transducing guanine nucleotide-binding proteins (G-proteins) are heterotrimeric plasma membrane-located proteins. The function of these proteins is to couple receptors for a wide variety of extracellular signalling molecules (neurotransmitters, peptide hormones and auto-and paracrine hormonal factors) to various intracellular signal-forming systems (for reviews see Rodbell, 1980; Stryer, 1986; Stryer and Bourne, 1986; Gilman, 1987; Birnbaumer et al., 1987; Casey and Gilman, 1988; Lochrie and Simon, 1988; Neer and Clapham, 1988; Chabre and Deterre, 1989; Gierschik et al., 1989a). The effector moieties regulated in their activity by G-proteins are either enzymes, e.g., the cyclic AMP-forming adenylate cyclase, the cyclic GMP-hydrolyzing phosphodiesterase in the retina or the polyphosphoinositidehydrolyzing phospholipase C, or ion channels. Compared to the number of receptors for extracellular signalling hormonal factors, being in the range of one hundred, the number of G-proteins, known so far both from the protein and cDNA level, is rather small, in the range of ten to fifteen. Some of these G-proteins are apparently widely distributed in different cell types of the mammalian organisms, e.g., the G_s- and G_i-proteins, while others exhibit a more restricted distribution, e.g., the G_o-proteins, which are apparently mainly localized in neuronal cells and tissues. Other G-proteins are even confined to one specialized cell type, e.g., the transducins, the G-proteins involved in light signal transduction by the photoexcited receptor rhodopsin.