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Phosducin is a protein kinase A-regulated G-protein regulator

Abstract

SIGNAL transduction by G-protein-coupled receptors is regulated by various mechanisms acting at the receptor level; those studied most thoroughly are from the β-adrenergic receptor/Gs/adenylyl cyclase system1–3. We report here a regulatory mechanism occurring at the level of the G proteins themselves. A protein with Mr 33,000 that inhibits Gs-GTPase activity was purified from bovine brain. This protein is very similar or identical to phosducin, a protein previously thought to be specific for retina and pineal gland4–8. Recombinant phosducin inhibited the GTPase activity of several G proteins, and also inhibited Gs-mediated adenylyl cyclase activation. Blockade of its inhibitory effects by protein kinase A suggests that phosducin may be part of a complex regulatory network controlling G-protein-mediated signalling.

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References

  1. Dohlman, H. G., Thorner, J., Caron, M. G. & Lefkowitz, R. J. A. Rev. Biochem. 60, 653–688 (1991).

    Article  CAS  Google Scholar 

  2. Hadcock, J. R. & Malbon, C. C. Trends Neurosci. 14, 242–247 (1991).

    Article  CAS  PubMed  Google Scholar 

  3. Lohse, M. J. in Signal Transmission in Photoreceptor Systems (eds Hargrave, P. A., Hofmann, K. P. & Kaupp, U. B.) 160–171 (Springer. Berlin, 1992).

    Book  Google Scholar 

  4. Lee, R. H., Lieberman, B. S. & Lolley, R. N. Biochemistry 26, 3983–3990 (1987).

    Article  CAS  PubMed  Google Scholar 

  5. Lee, R. H., Flower, A., McGinnis, J. F., Lolley, R. N. & Craft, C. M. J. biol. Chem. 265, 15867–15873 (1990).

    CAS  PubMed  Google Scholar 

  6. Kuo, C.-H. et al. Biochem. biophys. Res. Commun. 162, 1063–1068 (1989).

    Article  CAS  PubMed  Google Scholar 

  7. Abe, T. et al. Gene 91, 209–215 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Reig, J. A., Yu, L. & Klein, D. C. J. biol. Chem. 265, 5816–5824 (1990).

    CAS  PubMed  Google Scholar 

  9. Benovic, J. L., Mayor, F., Staniszewski, C., Lefkowitz, R. J. & Caron, M. G. J. biol. Chem. 262, 9026–9032 (1987).

    CAS  PubMed  Google Scholar 

  10. Benovic, J. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8879–8882 (1987).

    Article  ADS  CAS  Google Scholar 

  11. Lohse, M. J., Benovic, J. L., Codina, J., Caron, M. G. & Lefkowitz, R. J. Science 248, 1547–1550 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Lohse, M. J. et al. J. biol. Chem. 267, 8558–8564 (1992).

    CAS  PubMed  Google Scholar 

  13. Studier, F. W., Rosenberg, A. H., Dunn, J. J. & Dubendorff, J. W. Meth. Enzym. 185, 60–89 (1990).

    Article  CAS  PubMed  Google Scholar 

  14. Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 348, 125–132 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Birnbaumer, L. A. Rev. Pharmac. Toxic 30, 675–705 (1990).

    Article  CAS  Google Scholar 

  16. Lohse, M. J., Benovic, J. L., Caron, M. G. & Lefkowitz, R. J. J. biol. Chem. 265, 3202–3209 (1990).

    CAS  PubMed  Google Scholar 

  17. Roth, N., Campbell, P. T., Caron, M. G., Lefkowitz, R. J. & Lohse, M. J. Proc. natn. Acad. Sci. U.S.A. 88, 6201–6204 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Yatani, A. et al. Cell 61, 769–776 (1990).

    Article  CAS  PubMed  Google Scholar 

  19. Strittmatter, S. M., Valenzuela, D., Sudo, Y., Linder, M. E. & Fishman, M. C. J. biol. Chem. 266, 22465–22471 (1991).

    CAS  PubMed  Google Scholar 

  20. Lohse, M. J., Klotz, K.-N. & Schwabe, U. Molec. Pharmac. 30, 403–409 (1986).

    CAS  Google Scholar 

  21. Benovic, J. L., Shorr, R. G. L., Caron, M. G. & Lefkowitz, R. J. Biochemistry 23, 4519–4525 (1984).

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  23. Chirgwin, J. J., Przbyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  PubMed  Google Scholar 

  24. Bokoch, G. M., Katada, T., Northup, J. K., Ui, M. & Gilman, A. G. J. biol. Chem. 259, 3560–3567 (1984).

    CAS  PubMed  Google Scholar 

  25. Sternweis, P. C. & Robishaw, J. D. J. biol. Chem. 259, 13806–13813 (1984).

    CAS  PubMed  Google Scholar 

  26. Sugden, P. H., Holladay, L. A., Reimann, E. M. & Corbin, J. D. Biochem. J. 159, 409–422 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lee, R. H., Brown, B. M. & Lolley, R. N. J. biol. Chem. 265, 15860–15866 (1990).

    CAS  PubMed  Google Scholar 

  28. Freissmuth, M. & Gilman, A. G. J. biol. Chem. 264, 21907–21914 (1989).

    CAS  PubMed  Google Scholar 

  29. Lohse, M. J. J. biol. Chem. 265, 3210–3211 (1990).

    CAS  Google Scholar 

  30. Lohse, M. J., Lefkowitz, R. J., Caron, M. G. & Benovic, J. L. Proc. natn. Acad. Sci. U.S.A. 86, 3011–3105 (1989).

    Article  ADS  CAS  Google Scholar 

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Bauer, P., Müller, S., Puzicha, M. et al. Phosducin is a protein kinase A-regulated G-protein regulator. Nature 358, 73–76 (1992). https://doi.org/10.1038/358073a0

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