Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins [16]

John D. Hildebrandt, Ronald D. Sekura, Juan Codina, Ravi Iyengar, Charles R. Manclark, Lutz Birnbaumer

Research output: Contribution to journalLetterpeer-review

205 Scopus citations

Abstract

Adenylyl cyclases are under positive and negative control by guanine nucleotides and hormones1-3. Stimulatory responses are mediated by a guanine nucleotide- and Mg-binding regulatory component4-6 (N s), a protein that has been purified to homogeneity7-9. Inhibitory responses have been hypothesized1-3,10,11 to be mediated by an analogous regulatory component (Ni) distinct from N s, but definitive proof for this is lacking and these effects may result from modulation of Ns activity. Recently, Bordetella pertussis toxin has been shown12 to ADP-ribosylate a peptide that is not part of N s, and this coincides with attenuation of hormonal inhibition of adenylyl cyclase12-17. We show here that cyc- S49 cells contain a substrate for ADP-ribosylation by pertussis toxin and that the toxin alters GTP dependent inhibition of cyc- adenyl cyclase activity 18. As cyc- S49 cells do not contain Ns by several criteria5,19-24, we conclude that Ni is a distinct and separate regulatory component of adenylyl cyclase.

Original languageEnglish
Pages (from-to)706-709
Number of pages4
JournalNature
Volume302
Issue number5910
DOIs
StatePublished - 1983
Externally publishedYes

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