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Phosphorylation-regulated CI channel in CHO cells stably expressing the cystic fibrosis gene

Abstract

A CYCLIC AMP-stimulated choride conductance appears when the cystic fibres is gene is expressed in non-epithelial cells by infection with recombinant viruses1,2. Cyclic AMP-stimulated conductance in this system is mediated by the same ohmic, low-conductance Cl- channel as in human secretory epithelia2–4, but control of this channel by phosphorylation has not been directly demonstrated. Here we report the appearance of the low-conductance Cl- channel in Chinese hamster ovary cells after stable transfection with the cystic fibres is gene. The channel is regulated on-cell by membrane-permeant analogues of cAMP and off-cell by protein kinases A and C and by alkaline phosphatase. These results are further evidence that the cystic fibrosis transmembrane regulator is a Cl- channel which can be activated by specific phosphorylation events and inactivated by dephosphorylation; they reveal an unsuspected synergism between converging kinase regulatory pathways.

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References

  1. Anderson, M. P., Rich, D. P., Gregory, R. J., Smith, A. E. & Welsh, M. J. Science 251, 679–682 (1991).

    Article  ADS  CAS  Google Scholar 

  2. Kartner, N. et al. Cell 64, 681–691 (1991).

    Article  CAS  Google Scholar 

  3. Gray, M. A., Harris, A., Coleman, L. Greenwell, J. R. & Argent, B. E. Am. J. Physiol. 257, C240–C251 (1989).

    Article  CAS  Google Scholar 

  4. Tabcharani, J. A., Low, D., Elie, D. & Hanrahan, J. W. FEBS Lett. 270, 157–164 (1990).

    Article  CAS  Google Scholar 

  5. Bialojan, C. & Takai, A. Biochem. J. 256, 283–290 (1988).

    Article  CAS  Google Scholar 

  6. Riordan, J. R. et al. Science 245, 1066–1073 (1989).

    Article  ADS  CAS  Google Scholar 

  7. Shenolikar, S. & Nairn, A. C. Advances in Cyclic Nucleotide Protein Phosphorylation Research 23, 1–121 (1991).

    CAS  Google Scholar 

  8. Shuster, M. J., Camardo, J. S., Siegelbaum, S. A. & Kandel, E. R. Nature 313, 392–395 (1985).

    Article  ADS  CAS  Google Scholar 

  9. Cohen, P. A. Rev. Biochem, 58, 453–508 (1989).

    Article  CAS  Google Scholar 

  10. Herscheler, J., Kameyama, M., Trautwein, W., Mieskes, G. & Soeling, H. D. Eur. J. Biochem. 165, 261–266 (1987).

    Article  Google Scholar 

  11. Levitan, I. B., Chung, S. & Reinhart, P. H. Advances in Second Messenger and Phosphoprotein Research 24, 36–40 (1990).

    CAS  PubMed  Google Scholar 

  12. Gregory, R. J. et al. Nature 347, 382–386 (1990).

    Article  ADS  CAS  Google Scholar 

  13. Chang, E. B., Wang, N. S. & Rao, M. C. Am. J. Physiol. 249, C356–C361 (1985).

    Article  ADS  CAS  Google Scholar 

  14. Fondacaro, J. D. & Henderson, L. S. Am. J. Physiol. 249, G422–G426 (1985).

    CAS  PubMed  Google Scholar 

  15. Brum, G., Flockerzi, V., Hofmann, F., Osterreider, W. & Trautwein, W. Pfluegers Arch. ges. Physiol. 398, 147–154 (1983).

    Article  CAS  Google Scholar 

  16. Lacerda, A. E., Rampe, D. & Brown, A. M. Nature 335, 245–251 (1988).

    Article  ADS  Google Scholar 

  17. Jahr, H., Nastainczyk, W., Röhrkasten, A., Schneider, T. & Hofmann, F. Eur. J. Biochem. 178, 535–542 (1988).

    Article  Google Scholar 

  18. Palmiter, R. D. et al. Cell 50, 435–443 (1987).

    Article  CAS  Google Scholar 

  19. Glass, D. B. et al. J. biol. Chem. 264, 8802–8810 (1989).

    CAS  PubMed  Google Scholar 

  20. Hardie, G. Nature 335, 592–593 (1988).

    Article  ADS  CAS  Google Scholar 

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Tabcharani, J., Chang, XB., Riordan, J. et al. Phosphorylation-regulated CI channel in CHO cells stably expressing the cystic fibrosis gene. Nature 352, 628–631 (1991). https://doi.org/10.1038/352628a0

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