title: The inhibitory G protein G(i) identified as pertussis toxin-catalyzed ADP-ribosylation.
abstract: Pertussis toxin (PTX) produced by Bordetella pertussis was first introduced by Ui and his colleagues in research on signal transduction under the name islet-activating protein in 1979, when the mechanism of toxin-induced stimulation of insulin release from pancreatic islets was reported in the rat. The stimulatory effect of PTX in vivo results from the blockage of α(2)-adrenergic receptor-mediated inhibition of insulin release. The receptor-induced inhibition of cAMP formation was also abolished in pancreatic islets isolated from PTX-treated rats, suggesting that the toxin caused uncoupling of adenylyl cyclase inhibition from receptor stimulation. The action of PTX on isolated membranes required a cytosolic factor, nicotinamide adenine dinucleotide (NAD), and the uncoupling induced by PTX was shown to be due to the toxin-catalyzed ADP-ribosylation of a 41-kDa protein with NAD as another substrate. The 41-kDa PTX substrate was soon identified and purified as the α-subunit of the inhibitory G protein that transmits an inhibitory signal from membrane receptors to adenylyl cyclase. After demonstration of the molecular mechanism of PTX, the toxin was widely utilized as a probe for identifying and analyzing major αβγ-trimeric G proteins. Thus, PTX-sensitive G proteins appeared to carry positive and negative signals from many membrane receptors to a variety of effectors other than adenylyl cyclase.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–0033, Japan. katada@mol.f.u-tokyo.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D007328:Insulin; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases