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 journalArticle

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 Receptor and Signal Transduction Research
Volume4
Issue number1-6
DOIs
StatePublished - 1984
Externally publishedYes

Fingerprint

Pertussis Toxin
Adenylyl Cyclases
Adenosine Diphosphate
Membranes
GTP-Binding Proteins
Drug Receptors
Dissection
GTP Phosphohydrolases
NAD
Large scale systems
Nucleotides
Adenosine Triphosphate
Cell Membrane
Hormones
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Pharmacology

Cite this

Pertussis toxin-catalyzed ADP-ribosylation : Effects on the coupling of inhibitory receptors to the adenylate cyclase system. / Moss, Joel; Bruni, Paola; Hsia, Judith A.; Tsai, Su Chen; Watkins, Paul A; Halpern, Jane L.; Burns, Drusilla L.; Kanaho, Yasunori; Chang, Patrick P.; Hewlett, Erik L.; Vaughan, Martha.

In: Journal of Receptor and Signal Transduction Research, Vol. 4, No. 1-6, 1984, p. 459-474.

Research output: Contribution to journalArticle

Moss, Joel ; Bruni, Paola ; Hsia, Judith A. ; Tsai, Su Chen ; Watkins, Paul A ; Halpern, Jane L. ; Burns, Drusilla L. ; Kanaho, Yasunori ; Chang, Patrick P. ; Hewlett, Erik L. ; Vaughan, Martha. / Pertussis toxin-catalyzed ADP-ribosylation : Effects on the coupling of inhibitory receptors to the adenylate cyclase system. In: Journal of Receptor and Signal Transduction Research. 1984 ; Vol. 4, No. 1-6. pp. 459-474.
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