Regulation of Hormone Receptors and Adenylyl Cyclases by Guanine Nucleotide Binding N Proteins

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein Gi

“…Inhibition of adenylate cyclase, by Gi, is elicited both through the interaction of tr-Gi with adenylate cyclase and by the release of fl,7 subunits from Gi, which inhibits the dissociation of Gs by mass action [1][2][3].…”

“…Both of these G-proteins have been isolated and characterised as heterotrimers (a,fl,7) possessing apparently identical ~,7 subunits but with distinct tr-subunits. The ce-subunits of these two G-proteins can be identified separately using cholera and pertussis toxins, which cause the NAD+-dependent ADPribosylation of a-subunits of Gs and Gi, respectively [1][2][3]. Such toxins, however, can also interact with other G-proteins.…”

“…One example is the Gprotein Go, which is found in a number of cell types. This species is related to Gi in that it provides a substrate for ADP-ribosylation by pertussis toxin but, however, does not inhibit adenylate cyclase [1][2][3].…”

“…The functioning of many receptors is mediated through the action of distinct guanine nucleotide regulatory proteins (G-proteins), which serve to couple receptors to their appropriate signal generation system [1][2][3]. In the case of adenylate cyclase two distinct G-proteins are involved.…”

β‐Subunits of the human liver Gs/Gi signal‐transducing proteins and those of bovine retinal rod cell transducin are identical

“…G-proteins (also N-proteins) are a family of membrane GTPases responsible for the transduction of hormone or neurotransmitter receptor occupancy, which occurs on the outer surface of cells, into altered activity of an effector system, the active site of which is located on the inner surface of the plasma membrane of cells (reviews [1][2][3]). Of the seven or eight such G-proteins that currently can be defined, four have been purified to better than 90°7o purity: G~, the stimulatory regulatory component of adenylyl cyclase [4][5][6]; G~, the inhibitory regulatory component of adenylyl cyclase [7,8]; G, (also T or transducin), the mediator between photoactivation of rhodopsin and stimulation of cGMP-specific phosphodiesterase in outer segments of retinal rod cells [9-tl]; and the socalled G,,, a pertussis toxin substrate of neural origin able to interact with brain muscarinic receptors, but having an as yet undefined effector [12,13].…”