Pertussis toxin-catalyzed ADP-ribosylation: Effects on the coupling of inhibitory receptors to the adenylate cyclase system

Joel Moss, Paola Bruni, Judith A. Hsia, Su Chen Tsai, Paul A. Watkins, Jane L. Halpern, Drusilla L. Burns, Yasunori Kanaho, Patrick P. Chang, Erik L. Hewlett, Martha Vaughan

Research output: Contribution to journalArticlepeer-review

Abstract

The adenylate cyclase system consists of stimulatory and inhibitory hormone and drug receptors coupled through different GTP-binding proteins to a catalytic unit, responsible for the synthesis of cAMP from ATP. Pertussis toxin blocks the effect of inhibitory agonists on the catalytic unit by enzymatically inactivating the inhibitory GTP-binding protein (Gi). Study of the inhibitory arm of the cyclase system has been facilitated by the dissection of the overall process of hormonal inhibition of cAMP formation into a series of reactions characteristic of the individual protein components of this complex system; pertussis toxin has proven to be a useful tool with which to study these individual reactions. Exposure of cells or membranes to pertussis toxin in the presence of NAD results in ADP-ribosylation of a 41,000 Da subunit of Gi. ADP-ribosylation of Gi has a number of effects on the overall and partial reactions of the cyclase system, including a loss of a) hormonal inhibition of cAMP formation, b) hormonal stimulation of GTPase and c) agonist-induced release of membrane-bound guanyl nucleotides. In addition, in toxin-treated membranes, the affinity of inhibitory receptors for agonist but not antagonist is decreased with no significant change in receptor number.

Original languageEnglish (US)
Pages (from-to)459-474
Number of pages16
JournalJournal of Receptors and Signal Transduction
Volume4
Issue number1-6
DOIs
StatePublished - Jan 1 1984
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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