Ethanol and Cell Tyrosine Kinase

  • Shivendra D. Shukla
  • Cindy Y. Zhu
  • Ilsa I. Rovira
  • Archie W. ThurstonJr.


Virtually no part of the body is spared by the effects of ethanol. Cells are the primary targets (Alcohol and Health, NIAAA Report, 1990). Ethanol has long been known to affect cell metabolism and enzyme activities (Hawkins and Kalant, 1972). Ethanol is metabolized in cells predominantly to acetaldehyde which can cause damaging effects. One of the first interactions of ethanol on a cell is with the cell membrane (Goldstein and Chin, 1981; Sun and Sun, 1985; Taraschi and Rubin, 1985). There is evidence that ethanol in the concentration range 50–500 mM has influences on membrane fluidity (Harris and Schroeder, 1981). Further, the effects of ethanol on membranes can be more discrete as it modifies lateral and vertical lipid domains (Wood et al., 1989).


Tyrosine Kinase A431 Cell Tyrosine Kinase Activity Fetal Alcohol Syndrome Epidermal Growth Factor Receptor Tyrosine Kinase 
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. Aaronson, S.A., 1991, Growth factors and cancer, Science 254: 1146.PubMedCrossRefGoogle Scholar
  2. Alcohol and Health: Seventh Special Report to the U.S. Congress on Alcohol and Health, 1990, U. S. Department of Health and Human Services, PHS-NIAAA.Google Scholar
  3. Allan, A.M. and Harris, R.A., 1987, Acute and chronic ethanol treatments alter GABA receptor operated chloride channels, Pharmacol. Biochem. Behav. 27: 665.Google Scholar
  4. Alling, C., Gustavsson, L., Momsson, J. E., Benthin, G. and Anggard, E., 1984, Phosphatidylethanol formation in rat organs after ethanol treatment, Biochim. Biophys. Acta 793: 119.CrossRefGoogle Scholar
  5. Anderson, D., Koch, C.A., Grey, L., Ellis, C., Moran, M.F. and Pawson, T., 1990, Binding of SH2 domains of phospholipase C-γ1, GAP, and src to activated growth factor receptors, Science 250: 979.PubMedCrossRefGoogle Scholar
  6. Bode, D.C. and Molinoff, P.B., 1988, Effects of ethanol in vitro on the β-adrenergic receptor-coupled adenylate cyclase system, J. Pharm. Exp. Therap. 246: 1040.Google Scholar
  7. Buhrow, S. W., Cohen, S., Garbers, D. L. and Staros, J.V., 1983, Characterization of the interaction of 5′-p-fluorosulfonylbenzoyl adenosine with the epidermal growth factor receptor/protein kinase in A431 cell membranes, J. Biol. Chem. 258: 7824.PubMedGoogle Scholar
  8. Cantley, L.C., Auger, K.R., Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R. and Saltoff, S., 1991, Oncogenes and signal transduction, Cell 64: 281.PubMedCrossRefGoogle Scholar
  9. Carpenter, G., King, Jr., L. and Cohen, S., 1979, Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor, J. Biol. Chem. 254: 4884.PubMedGoogle Scholar
  10. Cochet, C., Filhol, O., Payrastre, B., Hunter, T. and Gill, G.N., 1991, Interactions between the EGF receptor and phosphoinositide kinase, J. Biol. Chem. 266: 637.PubMedGoogle Scholar
  11. Cohen, S., Ushiro, H., Stosheck, C. and Chinkers, M., 1982, A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles, J. Biol. Chem. 257: 1523.PubMedGoogle Scholar
  12. Collet, M.S. and Erikson, R.L., 1978, Protein kinase activity associated with the avian sarcoma virus src gene product, Proc. Natl. Acad. Sci. USA 75: 2021.CrossRefGoogle Scholar
  13. Crews, F.T., Pontzer, N.J. and Chandler, L. J., 1989, Effect of ethanol on receptors coupled to phosphoinositide hydrolysis in brain. In: Molecular Mechanisms of Alcohol: Neurobiology and Metabolism, G. Y. Sun et al, eds., Humana Press, p. 39.Google Scholar
  14. DePetrillo, P. B. and Swift, R. M., 1992, Ethanol exposure results in a transient decrease in human platelet cAMP levels: evidence for a protein kinase C mediated process. Alcoholism: Clinical and Experimental Research 16: 290.CrossRefGoogle Scholar
  15. Dhar, A., Paul, A. and Shukla, S.D., 1990, Involvement of tyrosine kinase in PAF stimulation of phsopholipase C in rabbit platelets: Studies with Genistein and monoclonal antibody of phosphotyrosine, Mol. Pharmacol. 37: 519.Google Scholar
  16. Dhar, A. and Shukla, S.D., 1991, Involvement of pp60c-src in PAF stimulated platelets: Evidence for translocation from cytosol to membranes, J. Biol. Chem. 266: 18797.PubMedGoogle Scholar
  17. Goldstein, D.B. and Chin, J.H., 1981, Interaction of ethanol with biological membranes, Fed. Proc. 40: 2073.Google Scholar
  18. Gonzales, R. A. and Crews, F. T., 1991, Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices, Alcohol 8: 131.PubMedCrossRefGoogle Scholar
  19. Grossman, C.J., Mendenhall, C.L. and Roseile, G.A., 1988, Alcohol and immune regulation: In vivo effects of ethanol on con-A sensitive thymic lymphocyte function, Int J. Immunopharm. 10: 187.CrossRefGoogle Scholar
  20. Harris, R.A. and Schroeder, F., 1981, Ethanol and the physical properties of brain membranes: Fluorescence studies, Mol. Pharmacol. 20: 128.Google Scholar
  21. Harris, R.A. and Allan, A.M., 1989, Alcohol intoxication: Ion channels and genetics. FASEB J. 3: 1689.PubMedGoogle Scholar
  22. Hawkins, R. D. and Kalant, H., 1972, The metabolism of ethanol and its metabolic effects, Pharmacol. Rev. 24: 67.Google Scholar
  23. Hoek, J.B., Thomas, A. P., Rooney, T. A., Higashi, K. and Rubin, E., 1992, Ethanol and signal transduction in the liver, FASEB J. 6: 2386.PubMedGoogle Scholar
  24. Hoffman, P.L., Moses, F., Luthin, G. R. and Tabakoff, B., 1986, Acute and chronic effects of ethanol on receptor-mediated phosphatidylinositol 4,5-bisphosphate breakdown in mouse brain, Mol. Pharmacol. 30: 13.Google Scholar
  25. Hoffman, P.L., Rabe, C.S., Moses, F. and Tabakoff, B., 1989, N-methyl-D-aspartate receptors and ethanol: Inhibition of calcium flux and cyclic GMP production. J. Neurochem. 52: 1937.PubMedCrossRefGoogle Scholar
  26. Hunt, W.A., Redos, J.D., Dalton, T.K. and Catravas, G.N., 1977, Alterations in brain c-GMP levels after acute and chronic treatment with ethanol, J. Pharm. Exp. Therap. 201: 103.Google Scholar
  27. Hunter, T. and Cooper, J.A., 1985, Protein tyrosine kinases, Ann. Rev. Biochem. 54: 897.PubMedCrossRefGoogle Scholar
  28. Jones, K. L. and Smith, D. W., 1973, Pattern of malformation in offspring in chronic alcoholic mothers, Lancet 1: 1267.PubMedCrossRefGoogle Scholar
  29. Kawamoto, T., Sato, J. D., Le, A., Polikoff, J., Sato, G. H. and Mendelsohn, J., 1983, Growth stimulation of A431 cells by epidermal growth factor: identification of high affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody, Proc. Natl. Acad. Sci. 80: 1337.PubMedCrossRefGoogle Scholar
  30. Kim, U.H., Fink, Jr., D., Kim, H.S., Park, D.J., Contreras, M.L., Guroff, G. and Rhee, S.G., 1991, Nerve growth factor stimulates phosphorylation of phospholipase C-γ in PC-12 cells, J. Biol. Chem. 266: 1359.PubMedGoogle Scholar
  31. Laemmli, U. K., 1970, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature (Lond.) 227: 680.CrossRefGoogle Scholar
  32. Lundquist, C., Rodriguez, F. D., Simonsson, P., Alling, C. and Gustavsson, L., 1992, Phosphatidylethanol and ethanol increase inositol 1,4,5-trisphosphate levels in NG108-15 neuroblastoma x glioma hybrid cells. Alcohol and Alcoholism 27: 61.Google Scholar
  33. Michaelis, E.K., Michaelis, M.L., Kumar, K.N., Tilakaratne, N., Joseph, D.B., Johnson, P.S., Babcock, K.K., Aistrup, G.L., Schowen, R.L., Minami, H., Sugawara, M., Odashima, K. and Umezawa, Y., 1992, Purification, reconstitution and cloning of an NMDA receptor-ion channel complex from rat brain synaptic membranes: implication for neurobiological changes in alcoholism, Ann. N.Y. Acad. Sci. 654: 7.PubMedCrossRefGoogle Scholar
  34. Nagy, L. E., Diamond, I., Casso, D. J., Franklin, C. and Gordon, A., 1990, Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter, J. Biol. Chem. 265: 1946.PubMedGoogle Scholar
  35. Nishibe, S., Wahl, M. I., Hernandez.Sotomayor, S.M.T., Tonks, N. K., Rhee, S. G. and Carpenter, G., 1990, Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation, Science 250: 1253.PubMedCrossRefGoogle Scholar
  36. Ouellette, E. M., Henry, R. L., Rosman, N. P. and Weiner, L., 1977, Adverse effects on offspring of maternal alcohol abuse during pregnancy, N. Engl. J. Med. 297: 528.PubMedCrossRefGoogle Scholar
  37. Rhee, S. G., 1991, Inositol phopsholipid-specific phospholipase C: interaction of the γ1 isoform with tyrosine kinase, Trends in Biochem. Sci. 16: 297.CrossRefGoogle Scholar
  38. Rubin, R., Ponnappa, B. C., Thomas, A. P. and Hoek, J. B., 1988, Ethanol stimulates shape change in human platelets by activation of phosphoinositide-specific phospholipase C, Arch. Biochem. Biophys. 260: 480.PubMedCrossRefGoogle Scholar
  39. Shukla, S.D., 1992, Platelet activating factor receptor and signal transduction mechanisms, FASEB J. 6: 2296.PubMedGoogle Scholar
  40. Shukla, S.D. and Halenda, S.P., 1991, Phospholipase C and D in receptor signalling. Life Sci. 48: 851.PubMedCrossRefGoogle Scholar
  41. Simonsson, P. and Alling, C., 1988, The 5-hydroxytryptamine stimulated formation of inositol phosphate is inhibited in platelets from alcoholics, Life Sci., 42: 385.PubMedCrossRefGoogle Scholar
  42. Simonsson, P., Sun, G. Y., Vecsei, L. and Alling, C., 1989, Ethanol effects on bradykinin-stimulated phosphoinositide hydrolysis in NG108-15 neuroblastoma-glioma cells. Alcohol 6: 475.PubMedCrossRefGoogle Scholar
  43. Snyder, A. K., Singh, S. P. and Ehmann, S., 1992, Effects of ethanol on DNA, RNA and protein synthesis in rat astrocyte cultures, Alcoholism: Clinical and Experimental Research 16: 295.CrossRefGoogle Scholar
  44. Sun, G. Y., Navidi, M., Yoa, F.-G. and Lin, T. N., 1991, Effects of acute and chronic ethanol administration on phosphoinositide metabolism in mouse brain, Alcohol and Alcoholism, Suppl. 1: 215.Google Scholar
  45. Sun, G.Y. and Sun, A.Y., 1985, State of the art review: Ethanol and membrane lipids, Alcoholism: Clin. Exp. Res. 9: 164.CrossRefGoogle Scholar
  46. Taraschi, T. F. and Rubin, E., 1985, Effects of ethanol on the chemical and structural properties of biologic membranes, Lab. Invest. 52: 120.Google Scholar
  47. Thurston, Jr., A.W. and Shukla, S.D., 1992a, Ethanol modulates basal and epidermal growth factor (EGF)-stimulated tyrosine kinase in A431 cell membranes, Alcohol and Alcoholism 27: 68.Google Scholar
  48. Thurston, Jr., A.W. and Shukla, S.D., 1992b, Ethanol modulates epidermal growth factor-stimulated tyrosine kinase and phosphorylation of PLC-γ1. Biochem. Biophys. Res. Commun. 185: 1062.CrossRefGoogle Scholar
  49. Tonks, N.K. and Charbonneau, H., 1989, Protein tyrosine dephosphorylation and signal transduction, Trends in Biochem. Sci. 14: 497.Google Scholar
  50. Ullrich, A. and Schlessinger, J., 1990, Signal transduction by receptors with tyrosine kinase activity, Cell 61: 203.PubMedCrossRefGoogle Scholar
  51. Walker, D.H., Dougherty, N. and Pike, L.J., 1988, Purification and characterization of a PI-kinase from A431 cells, Biochemistry 27: 6504.PubMedCrossRefGoogle Scholar
  52. Wang, S., Jacober, L., Wang, C., Slomiany, A. and Slomiany, B.L., 1992, Ethanol-induced structural and functional alterations of epidermal growth factor receptor in buccal mucosa. Int. J. Biochem. 24: 85.PubMedCrossRefGoogle Scholar
  53. Wood, W.G., Gorka, C. and Schroeder, F., 1989, Acute and chronic effects of ethanol on transbilayer membrane domains, J. Neurochem. 52: 1925.PubMedCrossRefGoogle Scholar
  54. Yarden, Y. and Ulrich, A., 1988, Growth factor receptor tyrosine kinase, Ann. Rev. Biochem. 57: 443.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Shivendra D. Shukla
    • 1
  • Cindy Y. Zhu
    • 1
  • Ilsa I. Rovira
    • 1
  • Archie W. ThurstonJr.
    • 1
  1. 1.Department of PharmacologyUniversity of Missouri-Columbia School of MedicineColumbiaUSA

Personalised recommendations