Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase (original) (raw)

Nature volume 314, pages 534–536 (1985)Cite this article

Abstract

Interaction of ligands with ‘Ca2+-mobilizing’ receptors is thought to result in the generation of two second messengers, inositol trisphosphate and diacylglycerol, from a common substrate, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (refs 1, 2), a component of plasma membranes3,4. It is not known how the occupation of such receptors is translated into the activation of the catalytic unit polyphosphoinositide (PPI) phosphodiesterase, and then to cellular activation, but our recent experiments suggest that GTP regulatory proteins may be involved. In mast cells, non-hydrolysable analogues of GTP introduced and then trapped in the cytosol are able to substitute for external ligands in inducing exocytosis, a well-defined Ca2+-dependent process5, suggesting that guanine nucleotide regulatory proteins may act by stimulating the catalytic activity of the PPI phosphodiesterase. We now provide evidence that mast cell secretion is inhibited by internalized neomycin, a compound known to interact with PPI6. We also show that the PPI phosphodiesterase of human neutrophil plasma membranes can be activated simply by adding GTP analogues in the presence of concentrations of Ca2+ that pertain in unstimulated cells. These findings strongly support the idea that the coupling factor linking receptor and PPI phosphodiesterase is a guanine nucleotide binding protein analogous to those involved in the activation and inhibition of adenylate cyclase7.

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References

  1. Michell, R. H. Trends pharmac. Sci. 8, 263–265 (1983).
    CAS Google Scholar
  2. Berridge, M. J. Biochem. J. 220, 345–360 (1984).
    Article CAS PubMed PubMed Central Google Scholar
  3. Downes, P. & Michell, R. H. Cell Calcium 3, 467–502 (1982).
    CAS PubMed Google Scholar
  4. Cockcroft, S., Taylor, J. & Judah, J. D. Biochim. biophys. Acta (in the press).
  5. Gomperts, B. D. Nature 306, 64–66 (1983).
    Article ADS CAS PubMed Google Scholar
  6. Schacht, J. J. Lipid Res. 19, 1063–1067 (1978).
    CAS PubMed Google Scholar
  7. Rodbell, M. Nature 284, 17–22 (1980).
    Article ADS CAS PubMed Google Scholar
  8. Bennett, J. P., Cockcroft, S. & Gomperts, B. D. J. Physiol., Lond. 317, 335–345 (1981).
    Article CAS PubMed PubMed Central Google Scholar
  9. Cockcroft, S., Baldwin, J. M. & Allan, D. Biochem. J. 221, 477–482 (1984).
    Article CAS PubMed PubMed Central Google Scholar
  10. Downes, C. P. & Michell, R. H. Biochem. J. 202, 53–58 (1982).
    Article CAS PubMed PubMed Central Google Scholar
  11. Downes, C. P., Mussat, M. C. & Michell, R. H. Biochem. J. 203, 169–177 (1982).
    Article CAS PubMed PubMed Central Google Scholar
  12. Remarks Concerning the Stability of GDP, GTP and dGTP (Boehringer Mannheim technical leaflet, 1984).
  13. Anderson, Q. S. & Murphy, R. C. J. Chromat. 121, 251–262 (1976).
    Article CAS Google Scholar
  14. Cockcroft, S. Biochim. biophys. Acta 795, 37–46 (1984).
    Article CAS PubMed Google Scholar
  15. Hyslop, P. A. et al. FEBS Lett. 166, 165–169 (1984).
    Article CAS PubMed Google Scholar
  16. Houslay, M. D. Trends biochem. Sci. 9, 39–40 (1984).
    Article CAS Google Scholar
  17. Nakamura, T. & Ui, M. FEBS Lett. 173, 414–418 (1984).
    Article CAS PubMed Google Scholar
  18. Okajima, F. & Ui, M. J. biol. Chem. 259, 13863–13871 (1984).
    CAS PubMed Google Scholar
  19. Kaziro, Y. Biochim. biophys. Acta 505, 95–127 (1978).
    Article CAS PubMed Google Scholar
  20. Stryer, L. Cold Spring Harb. Symp. quant. Biol. 48, 841–852 (1983).
    Article CAS PubMed Google Scholar
  21. Heyworth, C. M., Rawal, S. & Houslay, M. D. FEBS Lett. 154, 87–91 (1983).
    Article CAS PubMed Google Scholar
  22. Heyworth, C. M., Wallace, A. V. & Houslay, M. D. Biochem. J. 214, 99–110 (1983).
    Article CAS PubMed PubMed Central Google Scholar
  23. McGrath, J. P., Capon, D. J., Goeddel, D. V. & Levinson, A. D. Nature 310, 644–649 (1984).
    Article ADS CAS PubMed Google Scholar
  24. Newbold, R. Nature 310, 628–629 (1984).
    Article ADS CAS PubMed Google Scholar
  25. Bennett, J. P., Caswell, A. H., Cockcroft, S. & Gomperts, B. D. Biochem. J. 208, 801–808 (1982).
    Article CAS PubMed PubMed Central Google Scholar
  26. Downes, C. P. & Michell, R. H. Biochem. J. 198, 133–140 (1981).
    Article CAS PubMed PubMed Central Google Scholar

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Authors and Affiliations

  1. Department of Experimental Pathology, University College London, London, WC1E 6JJ, UK
    Shamshad Cockcroft & Bastien D. Gomperts

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  1. Shamshad Cockcroft
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  2. Bastien D. Gomperts
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Cockcroft, S., Gomperts, B. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase.Nature 314, 534–536 (1985). https://doi.org/10.1038/314534a0

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