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Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins

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 (Ns), 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 Ns, 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 Ns, 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 activity18. 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.

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Hildebrandt, J., Sekura, R., Codina, J. et al. Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins. Nature 302, 706–709 (1983). https://doi.org/10.1038/302706a0

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