Advertisement

The Journal of Membrane Biology

, Volume 106, Issue 3, pp 203–210 | Cite as

Growth factors modulate junctional cell-to-cell communication

  • Pedro E. Maldonado
  • Birgit Rose
  • Werner R. Loewenstein
Articles

Summary

The epidermal growth factor (EGF) and the platelet-derived growth factor (PDGF) inhibit gap junctional communication in the mammalian cell lines NRK and BalbC 3T3: cell-to-cell transfer of a 400-dalton tracer molecule is reduced and junctional conductance is reduced. The inhibition of cell-to-cell transfer is reversible and dose dependent; half-maximal effects are obtained at 10−9 and 10−11m concentrations of EGF and PDGF, respectively. The response of junctional conductance is detectable within 2 min of EGF application and reaches a maximum within 10 min. It is among the earliest cellular responses to this growth factor and may be significant in the regulation of growth. The response is lacking in EGF receptor-deficient NIH 3T3 cells. The transforming factor β (TGFβ) enhances junctional communication in BalbC 3T3: cell-to-cell transfer is increased over a period of 8 hr. But in NRK cells, where it upregulates EGF receptors, TGFβ reduces junctional communication synergistically with EGF.

Key Words

gap junction growth factors EGF PDGF TGFβ cell-to-cell communication junctional communication 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Assoian, R.K., Frolik, Ch.A., Roberts, A.B., Miller, D.M., Sporn, M.B. 1984. Transforming growth factor-β controls receptor levels for epidermal growth factor in NRK fibroblasts.Cell 36:35–41CrossRefPubMedGoogle Scholar
  2. Atkinson, M.M., Menko, A.S., Johnson, R.G., Sheppard, J.R., Sheridan, J.D. 1981. Rapid and reversible reduction of junctional permeability in cells infected with a temperature-sensitive mutant of avian sarcoma virus.J. Cell Biol. 91:573–578Google Scholar
  3. Azarnia, R., Loewenstein, W.R. 1984a. Intercellular communication and the control of growth: X. Alteration of junctional permeability by thesrc gene. A study with temperature-sensitive mutant Rous sarcoma virus.J. Membrane Biol. 82:191–205Google Scholar
  4. Azarnia, R., Loewenstein, W.R. 1984b. Intercellular communication and the control of growth: XI. Alteration of junctional permeability by thesrc gene in a revertant cell with normal cytoskeleton.J. Membrane Biol. 82:207–212Google Scholar
  5. Azarnia, R., Loewenstein, W.R. 1987. Polyomavirus middle T antigen downregulates junctional cell-to-cell communication.Mol. Cell Biol. 7:946–950PubMedGoogle Scholar
  6. Azarnia, R., Reddy, S., Kmiecik, T., Shalloway, D., Loewenstein, W.R. 1988a. The cellularsrc gene product regulates junctional cell-to-cell communication.Science 239:398–401PubMedGoogle Scholar
  7. Azarnia, R., Reddy, S., Kmiecik, T., Shalloway, D., Loewenstein, W.R. 1988b. The cellularsrc gene: Regulation of communication and growth.In: Gap Junctions. Modern Cell Biology Series. Vol. 7, pp. 423–433. E. Hertzberg and R. Johnson, editors A.R. Liss, New YorkGoogle Scholar
  8. Balk, S.D. 1971. Calcium as a regulator of the proliferation of normal, but not of transformed chicken fibroblasts in a plasma-containing medium.Proc. Natl. Acad. Sci. USA 68:271–275PubMedGoogle Scholar
  9. Carpenter, G., Cohen, S. 1979. Epidermal growth factor.Annu. Rev. Biochem. 48:193–216PubMedGoogle Scholar
  10. De Larco, J., Todaro, G.J. 1978. Growth factors from murine sarcoma virus-transformed cells.Proc. Natl. Acad. Sci. USA 75:4001–4005PubMedGoogle Scholar
  11. Flagg-Newton, J.L., Dahl, G., Loewenstein, W.R. 1981. Cell junction and cyclic AMP: I. Upregulation of junctional membrane permeability and junctional membrane particles by administration of cyclic nucleotide or phosphodiesterase inhibitor.J. Membrane Biol. 63:105–121Google Scholar
  12. Flagg-Newton, J.L., Simpson, I., Loewenstein, W.R. 1979. Permeability of the cell-to-cell membrane channels, in mammalian cell junction.Science 205:404–407PubMedGoogle Scholar
  13. Heldin, C.H., Westermark, B. 1984. Growth factors: Mechanism of action and relation to oncogenes.Cell 37:9–20PubMedGoogle Scholar
  14. Hesketh, T., Moore, J., Morris, J., Taylor, M., Rogers, J., Smith, G., Metcalfe, J. 1985. A common sequence of calcium and pH signals in the mitogenic stimulation of eukaryotic cells.Nature (London) 313:481–484Google Scholar
  15. Hunter, T., Cooper, J. 1985. Protein-tyrosine kinases.Annu. Rev. Biochem. 54:897–930PubMedGoogle Scholar
  16. Kumar, N.M., Gilula, N.B. 1986. Cloning and characterization of human and rat liver cDNAs coding for a junction protein.J. Cell Biol. 103:766–776Google Scholar
  17. Livneh, E., Prywes, R., Kashles, O., Reiss, N., Sasson, I., Mory, Y., Ullrich, A., Schlessinger, J. 1986. Reconstitution of human epidermal growth factor receptors and its deletion mutants in cultured hamster cells.J. Biol. Chem. 261:12490–12497PubMedGoogle Scholar
  18. Loewenstein, W.R. 1981. Junctional intercellular communication. The cell-to-cell membrane channel.Physiol. Rev. 61:829–913PubMedGoogle Scholar
  19. Loewenstein, W.R. 1985. Regulation of cell-to-cell communication by phosphorylation.Biochem. Soc. Symp. London 50:43–58Google Scholar
  20. Loewenstein, W.R. 1987. The cell-to-cell channels of gap junctions.Cell 48:725–726PubMedGoogle Scholar
  21. Massagué, J. 1987. The TGF-β family of growth and differentiation factors.Cell 49:437–438PubMedGoogle Scholar
  22. Massagué, J., Like, B. 1985. Cellular receptors for type β transforming growth factor.J. Biol. Chem. 260:2636–2645PubMedGoogle Scholar
  23. Mehta, P.P., Bertram, J., Loewenstein, W.R. 1988. The actions of retinoids on cellular growth correlate with their actions on gap junctional communication.J. Cell Biol (in press) Google Scholar
  24. Moolenar, W., Tertoolen, L., deLaat, S. 1984. Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts.J. Biol. Chem. 259:8066–8069PubMedGoogle Scholar
  25. Paul, D.L. 1986. Molecular cloning of cDNA for rat liver gap junction protein.J. Cell Biol. 103:123–134PubMedGoogle Scholar
  26. Radu, A., Dahl, G., Loewenstein, W.R. 1982. Hormonal regulation of cell junction permeability: Upregulation by catecholamine and prostagladin E1.J. Membrane Biol. 70:239–251Google Scholar
  27. Rose, B., Loewenstein, W.R. 1975. Permeability of cell junction depends on local cytoplasmic calcium activity.Nature (London) 254:250–252Google Scholar
  28. Rose, B., Yada, T., Loewenstein, W.R. 1986. Downregulation of cell-to-cell communication by the viralsrc gene is blocked by TMB-8 and recovery of communication is blocked by vanadate.J. Membrane Biol. 94:129–142Google Scholar
  29. Simpson, I., Rose, B., Loewenstein, W.R. 1977. Size limit of molecules permeating the junctional membrane channels.Science 195:294–296PubMedGoogle Scholar
  30. Socolar, S.J., Loewenstein, W.R. 1979. Methods for studying transmission through permeable cell-to-cell junctions.In: Methods in Membrane Biology. Vol. 10, pp. 123–179. E. Korn, editor. Plenum. New YorkGoogle Scholar
  31. Sporn, M.B., Roberts, A.B., Wakefield, L.M., Assoian, R.K. 1986. Transforming growth factor-β: Biological function and chemical structure.Science 233:532–534PubMedGoogle Scholar
  32. Tucker, R.F., Shipley, G.D., Moses, H.L., Holley, R.W. 1984. Growth inhibitor from BSC-1 cells closely related to platelet type β transforming growth factor.Science 226:705–707PubMedGoogle Scholar
  33. Unwin, P.N.T., Ennis, P.D. 1984. Two configurations of a channel-forming membrane protein.Nature (London) 307:609–613CrossRefGoogle Scholar
  34. Wiener, E.C., Loewenstein, W.R. 1983. Correction of cell-cell communication defect by introduction of a protein kinase into mutant cells.Nature (London) 305:433–435Google Scholar
  35. Yada, T., Rose, B., Loewenstein, W.R. 1985. Diacylglycerol downregulates junctional membrane permeability. TMB-8 blocks this effect.J. Membrane Biol. 88:217–232Google Scholar

Copyright information

© Springer-Verlag New York Inc 1988

Authors and Affiliations

  • Pedro E. Maldonado
    • 1
  • Birgit Rose
    • 1
  • Werner R. Loewenstein
    • 1
  1. 1.Department of Physiology and BiophysicsUniversity of Miami School of MedicineMiami

Personalised recommendations