Multiple sources of sn-1,2-diacylglycerol in mitogen-stimulated Swiss 3T3 cells; evidence for activation of phosphoinositidase C and PtdChophospholipase D

  • Simon J. Cook
  • Susan Palmer
  • Robin Plevin
  • Michael J. O. Wakelam
Conference paper
Part of the NATO ASI Series book series (volume 52)


A number of growth factors, exemplified by bombesin, bind to receptors and stimulate the hydrolysis of PtdIns(4,5)P2 to generate Ins(1,4,5)P3 and sn-1,2-diacylglycerol (DG) (reviewed by Berridge, 1987). These two molecules are potent second messengers: Ins(1,4,5)P3 binds to a specific receptor, probably on the E.R., stimulating the release of sequestered calcium into the cytosol (reviewed by Berridge & Irvine, 1989) whilst DG remains within the inner leaflet of the plasma membrane where it binds to and activates protein kinase C (reviewed by Parker et al., 1989). This pathway is implicated in the regulation of a number of the early events associated with entry into the cell cycle including increases in pHi (Hesketh et al., 1986), induction of the expression of c-fos and c-myc proto-oncogenes (Rozengurt & Sinnet-Smith, 1987) and activation of the ribosomal protein S6 kinase (Susa et al., 1989). However PtdIns(4,5)P2 hydrolysis is not a pre-requisite for stimulation of cell proliferation by all growth factors, e.g. EGF in Swiss 3T3 cells (Whitman & Cantley, 1988). In addition, it should be noted that the increase in Ins(1,4,5)P3 is essentially transient, as is the associated increase in [Ca2+]i, declining towards control within 1–2 minutes whereas DNA synthesis requires the continued presence of the mitogen for up to 8–10 hours.


Inositol Lipid Constant Specific Activity GTPase Activate Protein Activity Sequestered Calcium Phosphatidyltransferase Activity 
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.











protein kinase C


phospholipase C


phospholipase D


phorbol myristate acetate


PtdOH phosphohydrolase




phosphatidic acid




Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berridge, M.J. (1987) Biochim. Biophys Acta. 907, 33–45.PubMedGoogle Scholar
  2. Berridge, M.J. & Irvine, R.F. (1989) Nature (Lond) 341, 197–205.CrossRefGoogle Scholar
  3. Billah, M.M. & Anthes J.C. (1990) Biochem. J. 269, 281–291.PubMedGoogle Scholar
  4. Black, F.M. & Wakelam, M.J.O. (1990) Biochem. J. 266, 661–667.PubMedGoogle Scholar
  5. Bonser, R.W., Thompson, N.T., Randall, R.W. & Garland, L.G. (1989) Biochem. J. 264, 617–620.PubMedGoogle Scholar
  6. Brown, K.D., Blakeley, D.M., Hamon, M.H., Laurie, M.S. & Corp, A.N. (1987) Biochem. J. 245, 631–639.PubMedGoogle Scholar
  7. Brown, K.D., Littlewood, C.J. & Blakeley, D.M. (1990) Biochem. J. 270, 557–560.PubMedGoogle Scholar
  8. Castagna, M., Takai, Y., Sano, K., Kikkaw, U. & Nishizuka, Y. (1982) J. Biol. Chem. 257, 7847–7851.PubMedGoogle Scholar
  9. Collins, M.K.L. & Rozengurt, E. (1984) J. Cell. Physiol. 118, 133–142.PubMedCrossRefGoogle Scholar
  10. Cook, S.J. & Wakelam, M.J.O. (1989) Biochem. J. 263, 581–587.PubMedGoogle Scholar
  11. Cook, S.J., Palmer, S. Plevin, R. & Wakelam, M.J.O. (1990) Biochem. J. 265, 617–620.PubMedGoogle Scholar
  12. Corps, A.N., Rees, L.H. Brown, K.D. (1985) Biochem. J. 231, 781–784.PubMedGoogle Scholar
  13. Davis, P.D., Hill, C.H., Keech, E., Lawton, G., Nixon, J.S., Sedgwick, A.D., Wadsworth, J., Westmacott, D. & Wilkinson, S.E. (1989) FEBS Lett. 259, 61–63.PubMedCrossRefGoogle Scholar
  14. Epand, R.M., & Stafford A.R. (1990) Biochem. Biophys. Res. Commun. 171, 487–490.PubMedCrossRefGoogle Scholar
  15. Erusalimsky, J.D., Friedberg, I. & Rozengurt, E. (1988) J. Biol Chem. 263, 19188–19194.PubMedGoogle Scholar
  16. Hesketh, T.R., Moore, J.P., Morris, J.D.H., Taylor, M.V., Rogers, J. Smith, G.A. & Metcalfe, J.C. (1986) Nature (Lond)313, 481–484.CrossRefGoogle Scholar
  17. Heslop, J.P., Blakeley, D.M., Brown, K.D. Irvine, R.F. & Berridge, M.J. (1986) Cell 47, 703–709.PubMedCrossRefGoogle Scholar
  18. Huang, C. & Cabot, M.C. (1990) J. Biol. Chem. 265, 14858–14863.PubMedGoogle Scholar
  19. Isacke, C.M., Meisenhelder, J., Brown, K.D., Gould, K.L., Gould, S.J. & Hunter, T. (1986) EMBO. J. 5, 2889–2898.PubMedGoogle Scholar
  20. MacDonald, L.M., Mack, K.F., Williams, B.W., King, W.C. & Glomset, J.A. (1988) J. Biol. Chem. 263, 1584–1592.PubMedGoogle Scholar
  21. MacPhee, C.H., Drummond, A.H., Otto, A.M. & Jimenez de Asua, L. (1984) J. Cell. Physiol. 119, 35–40.PubMedCrossRefGoogle Scholar
  22. Martin, T.W. (1988) Biochim. Biophys. Acta. 962, 282–296.PubMedGoogle Scholar
  23. Matozaki, T., Göke, B, Tsunoda, T., Martinez, J., & Williams, J.A. (1990) J. Biol. Chem. 265, 6247–6254.PubMedGoogle Scholar
  24. Moolenaar, W.H., Kruijer, W., Tilley, B.C., Verlaan, I., Bierman, A.J., & de Laat, S.W. (1986) Nature (Lond) 323, 171–173.CrossRefGoogle Scholar
  25. Nanberg, E. & Rozengurt, E. (1988) EMBO. J. 7, 2741–2747.PubMedGoogle Scholar
  26. Ohno, S. Akita, Y. Konno, Y. Imajoh, S. & Suzuki, K. (1988) Cell. 53, 731–741.PubMedCrossRefGoogle Scholar
  27. Parker, P.J., Kour, G., Marais, R.M., Mitchell, F., Pears, C. Schaap, D., Stabel, S. & Webster, C. (1989) Mol. Cell. Endocrinol. 65, 1–11.PubMedCrossRefGoogle Scholar
  28. Palmer, S, Hughes, K.T., Lee, D.Y. & Wakelam, M.J.O. (1989) Cell. Signal. 1, 147–156.PubMedCrossRefGoogle Scholar
  29. Pessin, M.S. & Raben, D.M. (1989) J. Biol. Chem. 264, 8729–8738.PubMedGoogle Scholar
  30. Preiss, J., Loomis, C.R., Bishop, R.W., Stein, R., Niedel, J.E. & Bell, R.M. (1986) J. Biol. Chem. 261, 8597–8600.PubMedGoogle Scholar
  31. Rodriguez-Pena, A. & Rozengurt, E. (1984) Biochem. Biophys. Res. Commun. 120, 1053–1059.PubMedCrossRefGoogle Scholar
  32. Rozengurt, E. & Sinnet-Smith, J.W. (1987) J. Cell. Physiol. 131, 218–225.PubMedCrossRefGoogle Scholar
  33. Schaap, D. & Parker, P.J. (1990) J. Biol. Chem. 265, 7301–7307.PubMedGoogle Scholar
  34. Susa, M., Olivier, A.R., Fabbro, D. & Thomas, G. (1989) Cell. 57, 817–824.PubMedCrossRefGoogle Scholar
  35. Suzuki-Sekimori, R., Matuoka, K. Nagai, Y. & Takenawa, T. (1989) J. Cell. Physiol. 140, 432–438.PubMedCrossRefGoogle Scholar
  36. Takuwa, N. Takuwa, Y. & Rasmussen, H. (1987b) Biochem. J. 243, 647–653.PubMedGoogle Scholar
  37. Takuwa, N., Takuwa, Y., Yanagisawa, M.,Yamashita, K. & Masaki, T. (1989) J. Biol. Chem. 264, 7856–7861.PubMedGoogle Scholar
  38. Tsai, M.H., Yu, C.L., Wei, F.S. & Stacey, D.W. (1989) Science. 243, 522–526.PubMedCrossRefGoogle Scholar
  39. Wakelam, M.J.O. (1988) Current Topics In Membranes & Transport. Academic Press 32, 87–112.Google Scholar
  40. Warden, C.H. & Friedkin, M. (1985) J. Biol. Chem. 260, 6006–6011.PubMedGoogle Scholar
  41. Whitman, M. & Cantley, L. (1988) Biochim. Biophys. Acta. 948, 327–344.Google Scholar
  42. Wright, T.M., Rangan, L.A., Shin, H.S. & Raben, D.M. (1988) J. Biol. Chem. 263, 9374–9380.PubMedGoogle Scholar
  43. van Corven, E.J., Groenink, A., Jalink, K., Eicholtz, T. & Moolenaar, W.H. (1989) Cell. 59, 45–54.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Simon J. Cook
    • 1
  • Susan Palmer
    • 1
  • Robin Plevin
    • 1
  • Michael J. O. Wakelam
    • 1
  1. 1.Molecular Pharmacology Group, Institute of BiochemistryUniversity of GlasgowGlasgowScotland, UK

Personalised recommendations