Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases

Ronald Taussig, Wei Jen Tang, John R. Hepler, Alfred G. Gilman

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Abstract

The capacities of the α subunits of pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins) to inhibit different isoforms of mammalian adenylyl cyclases were assessed. Membranes from Sf9 cells infected with recombinant baculoviruses encoding either type I, II, V, or VI adenylyl cyclase were reconstituted with purified G protein subunits. Types V and VI adenylyl cyclase are most sensitive to inhibition by G(iα1), G(iα2), and G(iα3); type I adenylyl cyclase can be inhibited by these three G(iα) proteins and by G(oα) as well. Type II adenylyl cyclase appears to be immune to inhibition by these proteins. Examination of the effects of native and mutant G(iα) proteins, as well as analysis of competition for binding of G(sα) to adenylyl cyclases, indicate that at least certain adenylyl cyclases have independent sites for interaction with G(sα) (site 1, stimulatory) and G(iα) (site 2, inhibitory). High concentrations of G(iα) can interact with site 1 on types I and II adenylyl cyclase and activate the enzymes. Types I and II adenylyl cyclase also appear to have independent sites for interaction with G protein βγ subunits. The type I enzyme is strongly inhibited, while type II adenylyl cyclase is activated if G(sα) is also present.

Original languageEnglish (US)
Pages (from-to)6093-6100
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number8
StatePublished - Feb 25 1994

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Adenylyl Cyclases
GTP-Binding Proteins
Guanine Nucleotides
Carrier Proteins
Protein Subunits
Gi-Go GTP-Binding Protein alpha Subunits
Sf9 Cells
Baculoviridae
Pertussis Toxin
Enzymes
Proteins
Protein Isoforms
Membranes
adenylyl cyclase 1
adenylyl cyclase 6

ASJC Scopus subject areas

  • Biochemistry

Cite this

Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. / Taussig, Ronald; Tang, Wei Jen; Hepler, John R.; Gilman, Alfred G.

In: Journal of Biological Chemistry, Vol. 269, No. 8, 25.02.1994, p. 6093-6100.

Research output: Contribution to journalArticle

Taussig, R, Tang, WJ, Hepler, JR & Gilman, AG 1994, 'Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases', Journal of Biological Chemistry, vol. 269, no. 8, pp. 6093-6100.
Taussig, Ronald ; Tang, Wei Jen ; Hepler, John R. ; Gilman, Alfred G. / Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 8. pp. 6093-6100.
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