Gangliosides as Receptor Modulators

  • Eric G. Bremer
  • Sen-itiroh Hakomori
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 174)


A number of studies have postulated cell surface gangliosides to be receptors for various bioactive factors such as glycoprotein hormones,1–3 interferon,4–6 and bacterial toxins,7–9 based on the interaction of gangliosides with these bioactive factors or ganglioside modification of the cellular effect of these factors. These observations, however, do not necessarily prove or support the idea that gangliosides function as receptors for these factors. In fact, in most of these cases, the receptor has been subsequently characterized as a protein, and the binding to gangliosides is generally of much lower affinity and specificity. With the exception of cholera toxin binding to the oligosaccharide moiety of GM1,10 few examples of ganglioside receptors have been demonstrated. Our recent studies on the effect of gangliosides on cell growth have suggested that gangliosides may alter the binding of polypeptide growth factors to their receptors in an indirect way.


Thymidine Incorporation Thyrotropin Receptor Baby Hamster Kidney Cell Polypeptide Growth Factor Exogenous Ganglioside 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    B. R. Mullin, P. H. Fishman, G. Lee, Sm. M. Aloj, F. D. Ledley, R. J. Winand, L. D. Kohn, and R. O. Brady, Thyrotropin-ganglioside interactions and their relationship to the structure and function of thyrotropin receptors. Proc. Natl. Acad. Sci. USA 73:842 (1976).PubMedCrossRefGoogle Scholar
  2. 2.
    G. Lee, S. M. Aloj, R. O. Brady, and L. D. Kohn, The structure and function of glycoprotein hormone receptors: Ganglioside interactions with human chorionic gonadotropin, Biochem. Biophys. Res. Commun. 73:370 (1976).PubMedCrossRefGoogle Scholar
  3. 3.
    G. Lee. S. M. Aloj, and L. D. Kohn, The structure and function of glycoprotein hormone receptors: Ganglioside interactions with luteinizing hormone, Biochem. Biophys. Res. Commun. 77:434 (1977).PubMedCrossRefGoogle Scholar
  4. 4.
    F. Besancon, and H. Ankel, Binding of interferon to gangliosides, Nature (Lond.) 252:478 (1974).CrossRefGoogle Scholar
  5. 5.
    V. E. Vengris, R. H. Reynolds, M. D. Hollenberg, and P. M. Pitha, Interferon action: Role of membrane gangliosides, Virology 72:486 (1976).PubMedCrossRefGoogle Scholar
  6. 6.
    H. Ankel, C. Krishnamaurti, F. Besancon, S. Stefanos, and E. Falcoff, Mouse fibroblast (type I) and immune (type II) interferons: Pronounced differences in affinity for gangliosides and in antiviral and antigrowth effects on mouse leukemia L-1210R cells, Proc. Natl. Acad. Sci. USA 77:2528 (1974).CrossRefGoogle Scholar
  7. 7.
    A. M. Haywood, Characteristics of Sendai virus receptors in a model membrane, J. Mol. Biol. 83:427 (1974).PubMedCrossRefGoogle Scholar
  8. 8.
    J. Holmgren, L. Svennerholm, H. Elwing, P. Fredman, and O. Strannegard, Sendai virus receptor: Proposed recognition structure based on binding to plastic-adsorbed gangliosides, Proc. Natl. Acad. Sci. USA 77:1947 (1980).PubMedCrossRefGoogle Scholar
  9. 9.
    F. D. Ledley, G. Lee, L. D. Kohn, W. H. Habig, and M. C. Hardegree, Tetanus toxin interactions with thyroid plasma membranes, J. Biol. Chem. 252:4049 (1977).PubMedGoogle Scholar
  10. 10.
    P. Cuatrecasas, Interaction of Vibrio cholerae enterotoxin with cell membranes, Biochemistry 12:3547 (1973).PubMedCrossRefGoogle Scholar
  11. 11.
    S. Hakomori, Glycosphingolipids in cellular interaction, differentiation, and oncogenesis, Annu. Rev. Biochem. 50:733 (1981).PubMedCrossRefGoogle Scholar
  12. 12.
    R. A. Laine, and S. Hakomori, Incorporation of exogenous glycosphingolipids in plasma membranes of cultured hamster cells and concurrent change of growth behavior, Biochem. Biophys. Res. Commun. 54:1039 (1973).PubMedCrossRefGoogle Scholar
  13. 13.
    I. Icarel-Liepkalns, V. A. Liepkalns, A. J. Yates, and R. E. Stephens, Cell cycle phases of a novel human neural cell line and the effect of exogenous gangliosides, Biochem. Biophys. Res. Commun. 105:225 (1982).CrossRefGoogle Scholar
  14. 14.
    T. W. Keenan, E. Scmid, W. W. Franke, and H. Wiegandt, Exogenous glycosphingolipids suppress growth rate of transformed and untransformed 3T3 cells, Exp. Cell Res. 92:259 (1975).PubMedCrossRefGoogle Scholar
  15. 15.
    D. Barnes, and G. Sato, Methods for growth of cultured cells in serum-free medium, Anal. Biochem. 102:255 (1980).PubMedCrossRefGoogle Scholar
  16. 16.
    T. Macaig, B. Kelley, J. Cerundolo, S. Ilsley, P. R. Kelley, J. Gaudreau, and R. Forand, Hormonal requirements of baby hamster kidney cells in culture, Cell Biol. Int. Reports 4:43 (1980).CrossRefGoogle Scholar
  17. 17.
    E. Raines, and R. Ross, Platelet-derived growth factor. I. High yield purification and evidence for multiple forms, J. Biol. Chem. 257:5154 (1982).PubMedGoogle Scholar
  18. 18.
    D. F. Bowen-Pope, and R. Ross, Platelet-derived growth factor. II. Specific binding to cultured cells, J. Biol. Chem. 257:5161 (1982).PubMedGoogle Scholar
  19. 19.
    G. Scatchard, The attraction of proteins for small molecules and ions, Ann. N. Y. Acad. Sci. 51:660 (1949).CrossRefGoogle Scholar
  20. 20.
    E. G. Bremer, and S. Hakomori, GM3 ganglioside induces haster fibroblast growth inhibition in chemically-defined medium: Gangliosides may regulate growth factor receptor function, Biochem. Biophys. Res. Commun. 106:711 (1982).PubMedCrossRefGoogle Scholar
  21. 21.
    S. Batzri, and E. D. Korn, Single bilayer liposomes prepared without sonication, Biochim. Biophys. Acta 298:1015 (1973).PubMedCrossRefGoogle Scholar
  22. 22.
    S. Kanda, K. Inone, S. Nojima, H. Utsumi, and H. Wiegandt, Incorporation of spin-labeled ganglioside analogues into cell and liposomal membranes, J. Biochem. 91:1707 (1982).PubMedGoogle Scholar
  23. 23.
    P. H. Fishman, J. Moss, and M. Vaughan, Uptake and metabolism of gangliosides in transformed mouse fibroblasts: Relationship of ganglioside structure to choleragen response, J. Biol. Chem. 251:4490 (1976).PubMedGoogle Scholar
  24. 24.
    D. M. Marcus, and L. Cass, Glycosphingolipids with Lewis blood group activity: Uptake by human erythrocytes, Science 164:553 (1969).PubMedCrossRefGoogle Scholar
  25. 25.
    G. Schwarzmann, A simple and novel method for tritium labeling of gangliosides and other sphingolipids, Biochim. Biophys. Acta 529:106 (1978).PubMedGoogle Scholar
  26. 26.
    D. Gospodorowicz, Purification of a fibroblast growth factor from bovine pituitary, J. Biol. Chem. 250:2515 (1975).Google Scholar
  27. 27.
    S. Cohn, G. Carpenter, and L. King, Jr., Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity, J. Biol. Chem. 255:4834 (1979).Google Scholar
  28. 28.
    K. Glenn, D. F. Bowen-Pope, and R. Ross, Platelet-derived growth factor. III. Identification of platelet-derived growth factor receptor by affinity labeling, J. Biol. Chem. 257:5172 (1982).PubMedGoogle Scholar
  29. 29.
    F.J. Sharom, and C. W. M. Grant, A model for ganglioside behavior in cell membranes, Biochim. Biophys. Acta 507:280 (1978).PubMedCrossRefGoogle Scholar
  30. 30.
    C. A. Longwood, S. Hakomori, and T. H. Ji, A glycolipid and its associated proteins: Evidence by crosslinking of human erythrocyte surface components, FEBS Lett. 112:265 (1980).CrossRefGoogle Scholar
  31. 31.
    W. A. Valente, P. Vitti, Z. Yavin, E. Yavin, E. F. Grollman, R. S. Toccafondi, and L. D. Kohn, Monoclonal antibodies to the thyrotropin receptor: Stimulating and blocking antibodies derived from the lymphocytes of patients with Graves disease, Proc. Natl. Acad. Sci. USA 79:6680 (1982).PubMedCrossRefGoogle Scholar
  32. 32.
    L. S. Lee, and I. B. Weinstein, Tumor-promoting phorbol esters inhibit the binding of epidermal growth factor to cellular receptors, Science 202:313 (1978).PubMedCrossRefGoogle Scholar
  33. 33.
    M. Shoyab, and G. T. Todaro, Perturbation of membrane phospholipids alters the interaction between epidermal growth factor and its membrane receptors, Arch. Biochem. Biophys. 296:222 (1981).CrossRefGoogle Scholar
  34. 34.
    J. B. Baker, G. S. Barsh, D. H. Carney, and D. D. Cunningham, Dexamethasone modulates binding and action of epidermal growth factor in serum-free cell culture, Proc. Natl. Acad. Sci. USA 75:1882 (1978).PubMedCrossRefGoogle Scholar
  35. 35.
    E. Rozengurt, K. D. Brown, and P. Petticum, Vasopressin inhibition of epidermal growth factor binding to cultured mouse cells, J. Biol. Chem. 256:716 (1981).PubMedGoogle Scholar
  36. 36.
    C. Heldin, A. Wasteson, and B. Westemark, Interaction of platelet-derived growth factor with its fibroblast receptor: Demonstration of ligand degradation and receptor modulation, J. Biol. Chem. 257:4216 (1982).PubMedGoogle Scholar
  37. 37.
    D. F. Bowen-Pope, P. E. DiCorleto, and R. Ross, Interactions between the receptors for platelet-derived growth factors and epidermal growth factor, J. Cell Biol. 96:679 (1983).PubMedCrossRefGoogle Scholar
  38. 38.
    J. Schlessinger, A. B. Schreiber, A. Levi, I. Lax, T. Libermann, and Y. Yarden, Regulation of cell proliferation by epidermal growth factor, Critical Reviews in Biochemistry 14:93 (1983).PubMedCrossRefGoogle Scholar
  39. 39.
    J. Nishimura, J. S. Huang, and T. F. Duel, Platelet-derived growth factor stimulates tyrosine-specific protein kinase activity in Swiss mouse 3T3 cell membranes, Proc. Natl. Acad. Sci. USA 79:4303 (1982).PubMedCrossRefGoogle Scholar
  40. 40.
    J. Pouyssegur, J. C. Chambard, A. Franchi, S. Paris, and E. Van Obberghen-Schilling, Growth factor activation of an amiloride-sensitive Na+ /H+ exchange system in quiescent fibroblasts: Coupling to ribosomal protein S6 phosphorylation, Proc. Natl. Acad. Sci. USA 79:3935 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Eric G. Bremer
    • 1
  • Sen-itiroh Hakomori
    • 1
  1. 1.Fred Hutchinson Cancer Research CenterThe University of WashingtonSeattleUSA

Personalised recommendations