Letter | Published:

Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins

Naturevolume 302pages706709 (1983) | Download Citation

Subjects

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Cooper, D. M. F. FEBS Lett. 138, 157–163 (1982).

  2. 2

    Londos, C., Cooper, D. M. F. & Rodbell, M. Adv. Cyclic Nucleotide Res. 14, 163–170 (1981).

  3. 3

    Jakobs, K. H., Aktories, K. & Schultz, G. Adv. Cyclic Nucleotide Res. 14, 173–187 (1981).

  4. 4

    Pfeuffer, T. J. biol. Chem. 252, 7224–7234 (1977).

  5. 5

    Ross, E. M. & Gilman, A. G. J. biol. Chem. 252, 6966–6969 (1977).

  6. 6

    Iyengar, R. & Birnbaumer, L. Proc. natn. Acad. Sci. U.S.A. 79, 5179–5188 (1982).

  7. 7

    Northrup, J. K. et al. Proc. natn. Acad. Sci. U.S.A. 77, 6516–6520 (1980).

  8. 8

    Sternweis, P. C., Northrup, J. K., Smigel, M.D. & Gilman, A. G. J. biol. Chem. 256, 11517–11526 (1981).

  9. 9

    Hanski, E., Sternweis, P. C., Northup, J. K., Dromerick, A. W. & Gilman, A. G. J. biol. Chem. 256, 12911–12919 (1981).

  10. 10

    Motulsky, H. J. et al. Proc. natn. Acad. Sci. U.S.A. 79, 4193–4197 (1982).

  11. 11

    Smith, S. K. & Limbrid, L. E. J. biol. Chem. 257, 10471–10478 (1982).

  12. 12

    Katada, T. & Ui. M. Proc. natn. Acad. Sci. U.S.A. 79, 3129–3133 (1982); J. biol. Chem. 257, 7210–7216 (1982).

  13. 13

    Hazeki, O. & Ui, M. J. biol. Chem. 256, 2856–2862 (1980).

  14. 14

    Katada, T. & Ui, M. J. biol. Chem. 256, 8310–8317 (1981).

  15. 15

    Cronin, M. J., Myers, G. A., Dabney, L. G. & Hewlett, E. L. Progrm 64th A. Meet. Endocr. Soc., A857 (1982).

  16. 16

    Garcia-Sainz, J. A. FEBS Lett. 126, 306–308 (1981).

  17. 17

    Katada, T. & Ui, M. J. biol. Chem. 255, 9580–9588 (1980).

  18. 18

    Hildebrandt, J. D., Hanoune, J. & Birnbaumer, L. J. biol Chem. 257, 14723–14725 (1982).

  19. 19

    Bourne, H. R., Coffino, P. & Tomkins, G. M. Science 187, 750 (1975).

  20. 20

    Johnson, G. L., Kaslow, H. R. & Bourne, H. R. Proc. natn. Acad. Sci. U.S.A. 75, 3113–3117 (1978).

  21. 21

    Ferguson, K. M., Northup, J. K. & Gilman, A. G. Fedn Proc. 41, 1407 (1982).

  22. 22

    Johnson, G. L., Kaslow, H. R. & Bourne, H. R. J. biol. Chem. 253, 7120–7123 (1978).

  23. 23

    Bird, S. J. & Maguire, M. E. J. biol. Chem. 253, 8826–8834 (1978).

  24. 24

    Ross, E. M., Maguire, M. E., Sturgill, T. W., Biltonen, R. L. & Gilman, A. G. J. biol. Chem. 252, 5761–5775 (1977).

  25. 25

    Lai, E., Rosen, O. M. & Rubin, C. S. J. biol. Chem. 256, 12866–12874 (1981).

  26. 26

    Kaslow, H. R., Johnson, G. L., Brothers, V. M. & Bourne, H. R. J. biol. Chem. 255, 3736–3741 (1980).

  27. 27

    Stadel, J. M., Shorr, R. G. L., Limbird, L. E. & Lefkowitz, R. J. J. biol. Chem. 256, 8718–8723 (1981).

  28. 28

    Cassel, D. & Pfeuffer, T. Proc. natn. Acad. Sci. U.S.A. 75, 2669–2673 (1978).

  29. 29

    Gill, D. M. & Meren, R. Proc. natn. Acad. Sci. U.S.A. 75, 3050–3054 (1978).

  30. 30

    Krawietz, W., Werdan, K. K. & Erdmann, E. Biochem. Pharmac. 31, 2463–2469 (1962).

  31. 31

    Cooper, D. M. F., Jagus, R., Somers, R. L. & Rodbell, M. Biochem. biophys. Res. Commun. 101, 1179–1185 (1981).

  32. 32

    Malbon, C. G. & Greenberg, M. L. J. clin. Invest. 69, 414–426 (1981).

  33. 33

    Aktories, K. & Jakobs, K. H. FEBS Lett. 130, 235–238 (1981).

  34. 34

    Koski, G. & Klee, W. A. Proc. natn. Acad. Sci. U.S.A. 78, 4185–4189 (1981).

  35. 35

    Cassel, D. & Salinger, Z. Biochim. biophys. Acta 452, 538–551 (1976).

  36. 36

    Bourne, H. R., Coffino, P. & Tomkins, G. M. J. cell. Physiol. 85, 603–610 (1975).

  37. 37

    Laemmli, U. Nature 227, 680–685 (1970).

  38. 38

    Cowell, J. L., Sato, Y., Sato, H., Amderlan, B. & Manclark, C. R. in Semin, in Infectious Disease Vol. 4 (eds Robbins, J., Hill, J. & Sadoff, J.) 371–379 (Thieme-Stratton, New York, 1982).

  39. 39

    Irons, L. I. & MacLennan, P. Biochim. biophys. Acta 580, 175–185 (1979).

  40. 40

    Yajima, M. et al. J. Biochem., Tokyo 83, 295–303 (1978).

  41. 41

    Meyer, S. L. Data Analysis for Scientists and Engineers, 39–41 (Wiley, New York, 1975).

Download references

Author information

Affiliations

  1. Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    • John D. Hildebrandt
    • , Juan Codina
    • , Ravi Iyengar
    •  & Lutz Birnbaumer
  2. Pertussis Branch, Division of Bacterial Products, National Center from Drugs and Biologies, Food and Drug Administration, Bethesda, Maryland, 20205, USA

    • Ronald D. Sekura
    •  & Charles R. Manclark

Authors

  1. Search for John D. Hildebrandt in:

  2. Search for Ronald D. Sekura in:

  3. Search for Juan Codina in:

  4. Search for Ravi Iyengar in:

  5. Search for Charles R. Manclark in:

  6. Search for Lutz Birnbaumer in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/302706a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.