Three Forms of Gi Discriminated by Synthetic Peptide Antisera
Two signal transduction pathways that are regulated by guanine nucleotide-binding proteins (G proteins) have been well characterized: the light-stimulated visual cascade and the hormone-sensitive adenylyl cyclase system (for review see Stryer, 1986; Gilman, 1987). Stimulation of retinal cyclic GMP phosphodiesterase by the photoreceptor rhodopsin is mediated by the G protein Gt (also referred to as transducin). Hormone-sensitive adenylyl cyclase is under dual stimulatory and inhibitory control by two other G proteins, Gs and Gi Receptors that stimulate adenylyl cyclase are coupled to the enzyme by Gg, whereas inhibitory receptors are coupled by Gi. These classical G proteins exhibit a characteristic heterotrimeric subunit structure. The ß and γ subunits are tightly associated with each other and in some cases are functionally interchangeable between different α subunits. The α subunits display more structural heterogeneity and functional specificity, and thus they serve to distinguish the different G protein oligomers. The α subunits possess a high-affinity binding site for guanine nucleotides and an intrinsic GTPase activity that are involved in the activation and deactivation of the G protein. Toxins from Vibrio cholerae and Bordetella pertussis are capable of covalently modifying and functionally altering a subunits. Cholera toxin catalyzes the ADP-ribosylation of Gs and Gt. ADP-ribosylation by pertussis toxin blocks activation of Gt and Gi by receptors. Activation of G proteins in detergent solution (and Gt in phospholipid vesicles) by nonhydrolyzable analogs of GTP involves dissociation of the α subunit from βγ. It is the α subunits of Gs and Gt (αs and αt) that stimulate their respective effector enzymes.
KeywordsAdenylyl Cyclase Guanine Nucleotide Pertussis Toxin Bovine Brain Rabbit Liver
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