Cell Membranes pp 365-405 | Cite as

Early Cytoplasmic Signals and Cytoskeletal Responses Initiated by Growth Factors in Cultured Cells

  • Paul L. McNeil
  • D. Lansing Taylor

Abstract

Growth factors activate quiescent cells in a stimulus-response coupling process that is initiated by binding the growth factor to its receptor on the cell surface (see Carpenter, 1984). The ultimate result of such activation is DNA synthesis and cell division (mitogenesis). However, such activated cells exhibit a host of earlier responses, some of which begin seconds poststimulation. These “early” cellular responses to growth factors include endocytosis, changes in the cytoskeleton, cell motility, phospholipid turnover, Na+/H+ exchanger activation, fluxes of a variety of ions, calcium transients, protein synthesis, changes in cyclic nucleotide levels, phosphorylation of specific proteins, and gene transcription. The connection, if any, of these early cellular responses with the later DNA synthetic response is obscure at present.

Keywords

Hydrolysis Lithium Lipase Adenosine Testosterone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ambros, V., Chen, L., and Buchanan, J., 1975, Surface ruffles as markers for studies of cell transformation by Rous sarcoma virus, Proc. Natl. Acad. Sci. USA 72:144–148.Google Scholar
  2. Ash, J., Voyt, P., and Singer, S., 1976, Reversion from transformed to normal pheno-type by inhibition of protein synthesis in rat kidney cells infected with a temperature-sensitive mutant of Rous sarcoma virus, Proc. Natl. Acad. Sci. USA 73:3603–3607.PubMedGoogle Scholar
  3. Axelrod, D., Keppel, D., Schlessinger, J., Elson, E., Webb, W., 1976, Mobility measurements by analysis of fluorescence photobleaching recovery kinetics, Biophysics 16:1055–1060.Google Scholar
  4. Balk, S. D., Whitfield, J. F., Youdale, T., and Braun, A. C., 1973, Roles of calcium, serum, plasma, and folic acid in the control of proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts, Proc. Natl. Acad. Sci. USA 70:675–679.PubMedGoogle Scholar
  5. Beguinot, L., Hanover, J. A., Ito, S., Richert, N. D., Willingham, M. C., and Paston, I., 1985, Phorbol esters induce transient internalization without degradation of unoccupied epidermal growth factor receptors, Proc. Natl. Acad. Sci. USA 82:2774–2778.PubMedGoogle Scholar
  6. Berridge, M. J., and Irvine, R. F., 1984, Inositol triphosphate, a novel second messenger in cellular signal transduction, Nature 312:315–321.PubMedGoogle Scholar
  7. Berridge, M. J., Downes, C. P., and Hanley, M. R., 1982, Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands, Biochem. J. 206:587–595.PubMedGoogle Scholar
  8. Berridge, M. J., Heslop, J. P., Irvine, R. F. and Brown, K. D., 1984a, Inositol lipids and cell proliferation, Biochem. Soc. Trans. 13:67–71.Google Scholar
  9. Berridge, M. J., Heslop, J. P., Irvine, R. F., and Brown, K. D., 1984b, Inositol triphosphate formation and calcium mobilization in Swiss 3T3 cells in response to platelet-derived growth factor, Biochem. J. 222:195–201.PubMedGoogle Scholar
  10. Besterman, J. M., and Cuatrecasas, P., 1984, Phorbol esters rapidly stimulate amiloride-sensitive Na+/H+ exchange in a human leukemic cell line, J. Cell Biol. 99:340–343.PubMedGoogle Scholar
  11. Betsholtz, C., and Westermark, B., 1984, Growth factor-induced proliferation of human fibroblasts in serum-free culture depends on cell density and extracellular calcium concentration, J. Cell Physiol. 118:203–210.PubMedGoogle Scholar
  12. Blackshear, P. J., Witters, L. A., Girard, P. R., Kuo, J. F., and Quama, S. N., 1985, Growth factor-stimulated protein phosphorylation in 3T3-L1 cells. Evidence for protein kinase C-dependent and -independent pathways, J. Biol. Chem. 260:13304–13315.PubMedGoogle Scholar
  13. Bockus, B., and Stiles, C., 1984, Regulation of cytoskeletal architecture by platelet-derived growth factor, insulin, and epidermal growth factor, Exp. Cell Res. 153:186–197.PubMedGoogle Scholar
  14. Bolton, T. B., 1979, Mechanisms of action of transmitters and other substances on smooth muscle, Physiol. Rev. 59:607–618.Google Scholar
  15. Boreiko, C., Mondal, S., Narajan, K., and Heidelberger, C, 1980, Effect of 12-O-tetradecanoyl-phorbol-13-acetate on the morphology and growth of C3H/10T1/2 mouse embryo cells, Cancer Res. 40:4709–4716.PubMedGoogle Scholar
  16. Boron, W. F., 1984, Cell activation: The “basic” connection, Nature 312:312.PubMedGoogle Scholar
  17. Bottom, T., 1974, Mechanisms of action of transmitters and other substances on smooth muscle, Physiol. Rev. 59:606–718.Google Scholar
  18. Bowen-Pope, D. F., and Ross, R., 1982, Platelet-derived growth factor. II. Specific binding to cultured cells, J. Cell Biol. 96:679–683.Google Scholar
  19. Bowen-Pope, D. F., and Rubin, H., 1983, Growth stimulatory precipitates of Ca2+ and pyrophosphate, J. Cell. Physiol. 117:51–61.PubMedGoogle Scholar
  20. Boynton, A. L., and Whitfield, J. F., 1976, The different actions of normal and supranormal calcium concentrations on the proliferation of Balb/c 3T3 mouse cells, In Vitro 12:479–484.PubMedGoogle Scholar
  21. Boynton, A., and Whitfield, J., 1983, The role of cyclic AMP in cell proliferation: A critical assessment of the evidence, Adv. Cyclic Neucleotide Res. 15:193–294.Google Scholar
  22. Boynton, A. L., Whitfield, J. F., Isaacs, R. J., and Morton, H. J., 1974, Control of 3T3 cell proliferation by calcium. In Vitro 10:12–17.PubMedGoogle Scholar
  23. Boynton, A. L., Whitfield, J. F., and Isaacs, R. J., 1976, The different roles of serum and calcium in the control of proliferation of Balb/c 3T3 mouse cells, In Vitro 12:120–123.PubMedGoogle Scholar
  24. Bretscher, A., and Lynch, W., 1985, Identification and localization of immunoreactive forms of caldesmon in smooth and nonmuscle cells: A comparison with the distributions of tropomyosin and α-actinin, J. Cell Biol. 100:1656–1663.PubMedGoogle Scholar
  25. Burns, C. P., and Rozengurt, E., 1983, Serum, platelet-derived growth factor, vassopressin, and phorbol esters increase intracellular pH in Swiss 3T3 cells, Biochem. Biophys. Res. Commun. 116:931–938.PubMedGoogle Scholar
  26. Burridge, K., and Feramisco, J., 1981, Non-muscle α-actinins are calcium sensitive actin-binding proteins, Nature 294:565–567.PubMedGoogle Scholar
  27. Burroni, D., and Ceccarini, C., 1984, The effect of alkaline pH on the cell growth of six different mammalian cells in tissue culture, Exp. Cell Res. 150:505–508.PubMedGoogle Scholar
  28. Busa, W. B., and Nuccitelli, R., 1984, Metabolic regulation via intracellular pH, Am. J. Physiol. 246:R409–R438.PubMedGoogle Scholar
  29. Campbell, A. K., 1983, Intracellular calcium. Its Universal Role as Regulator ,John Wiley and Sons, New York, p. 556.Google Scholar
  30. Carney, D. H., Scott, D. L., Gordon, E. A., and LaBelle, E. F., 1985, Phosphoinositides in mitogenesis: Neomysin inhibits thrombin-stimulated phosphoinositide turnover and initiation of cell proliferation, Cell 42:479–488.PubMedGoogle Scholar
  31. Carpenter, G., 1984, Properties of the receptor for epidermal growth factor, Cell 37:357–358.PubMedGoogle Scholar
  32. Carpenter, G., and Cohen, S., 1976, 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts, J. Cell Biol. 71:159–171.PubMedGoogle Scholar
  33. Carpenter, G., and Cohen, S., 1979, Epidermal growth factor, Annu. Rev. Biochem. 48: 193–216.PubMedGoogle Scholar
  34. Carpenter, G., and Cohen, S., 1984, Peptide growth factors, Trends Biochem. Sci. 9:169–171.Google Scholar
  35. Cassel, D., Whiteley, B., Zhuang, Y. X., and Glaser, L., 1985, Mitogen-independent activation of Na+/H+ exchange in human epidermoid carcinoma A431 cells: Regulation by medium osmolality, J. Cell Physiol. 122:178–186.PubMedGoogle Scholar
  36. Ceccarini, C., and Eagle, H., 1971a, pH as a determinant of cellular growth and contact inhibition, Proc. Natl. Acad. Sci. USA 68:229–233.PubMedGoogle Scholar
  37. Ceccarini, C. and Eagle, H., 1971b, Induction and reversal of contact inhibition of growth by pH modification, Nature New Biol. 233:271–273.PubMedGoogle Scholar
  38. Chinkers, M., McKenna, J., and Cohen, S., 1979, Rapid induction or morphological changes in human carcinoma cells A-431 by epidermal growth factor, J. Cell Biol. 83:260–265.PubMedGoogle Scholar
  39. Chinkers, M., McKenna, J., and Cohen, S., 1981, Rapid rounding of human epidermoid carcinoma cells A-431 induced by epidermal growth factor, J. Cell Biol. 88:422–429.PubMedGoogle Scholar
  40. Cochet, C., Gill, G. N., Meisenhelder, J., Cooper, J. A., and Hunter, T., 1984, C-kinase phos-phorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity, J. Biol. Chem. 259:2553–2558.PubMedGoogle Scholar
  41. Cohen, P., 1982, The role of protein phosphorylation in neural and hormonal control of cellular activity, Nature 296:613–620.PubMedGoogle Scholar
  42. Cohen, S., Carpenter, G.,and King, L., 1980, Epidermal growth factor-receptor-proteinkinase interactions, J. Biol. Chem. 255:4834_4842.PubMedGoogle Scholar
  43. Cooper, J. A., Bowen-Pope, D. F., Raines, E., Ross, R., and Hunter, T., 1982, Similar effects of platelet-derived growth factor and epidermal growth factor on the phosphorylation of tyrosine in cellular proteins, Cell 31:263–273.PubMedGoogle Scholar
  44. Cooper, J. A., Sefton, B. M., and Hunter, T., 1984, Diverse mitogenic agents induce the phosphorylation of two related 42,000 dalton proteins on tyrosine in quiescent cells, Mol. Cell. Biol. 4:30–37.PubMedGoogle Scholar
  45. Croy, R., and Pardee, A. B., 1979, Enhanced synthesis and stabilization of Mr 68,000 protein in transformed Balb/c-3T3 cells: Candidate for restriction point control of cell growth, Proc. Natl. Acad. Sci. USA 80:4699–4703.Google Scholar
  46. Dale, M. M., and Penfield, A., 1984, Synergism between phorbol ester and A23187 in superoxide production by neutrophils, Fed. Eur. Biochem. Sci. 175:170–178.Google Scholar
  47. Das, M., and Fox, C. F., 1978, Molecular mechanism of mitogen action: Processing of receptor induced by epidermal growth factor, Proc. Natl. Acad. Sci. USA 75:2644–2648.PubMedGoogle Scholar
  48. Dicker, P., and Rozengurt, E., 1980, Phorbol esters and vassopressin stimulate DNA synthesis by a common mechanism, Nature 287:607–612.PubMedGoogle Scholar
  49. Diringer, H., and Friis, R. R., 1977, Changes in phosphatidylinositol metabolism correlated to growth state of normal and Rous sarcoma virus-transformed Japanese quail cells, Cancer Res. 37:2978–2984.Google Scholar
  50. Downes, C. P., and Michell, R. H., 1981, The polyphosphoinositide phosphodiesterase of erythorocyte membranes, Biochem. J. 198:133–140.PubMedGoogle Scholar
  51. Drummond, A. H., 1985, Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells, Nature 315:752–755.PubMedGoogle Scholar
  52. Dulbecco, R., Elkington, J., 1975, Induction of growth in resting fibroblastic cell cultures by Ca2+, Proc. Natl. Acad. Sci. USA 72:1584–1588.PubMedGoogle Scholar
  53. Edelman, G., 1976, Surface modulation in cell recognition and cell growth, Science 192:218.PubMedGoogle Scholar
  54. Edelman, G., and Yahara, I., 1976, Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus, Proc. Natl. Acad. Sci. USA 73:2047–2051.PubMedGoogle Scholar
  55. Ek, B., Westermark, B., Wasteson, A., and Heldin, C. H., 1982, Stimulation of tyrosine-specific phosphorylation by platelet derived growth factor, Nature 295:419–420.PubMedGoogle Scholar
  56. Engstrom, W., Zetterberg, A., and Auer, G., 1982, Calcium, phosphate, and cell proliferation, in: Ions, Cell Proliferation, and Cancer (A. L. Boynton, W. L. McKeehan, and J. F. Whitfield, eds.), Academic Press, New York, pp. 259–281.Google Scholar
  57. Fechheimer, M., Brier, J., Rockwell, M., Luna, E., and Taylor, D., 1982, A calcium and pH regulated actin binding protein from D. discoideum, Cell Motility 2:287–308.Google Scholar
  58. Gail, M., Scher, C., and Boone, C, 1972, Dissociation of cell motility from cell proliferation in BALB/C-3T3 fibroblasts, Exp. Cell Res. 70:439–443.PubMedGoogle Scholar
  59. Gey, C, 1955, Some aspects of the constitution and behavior of normal and malignant cells maintained in continuous culture, Harvey Lect. 50:154–229.Google Scholar
  60. Gillies, R. J., 1981, Intracellular pH and growth control in eukaryotic cells, in: The Transformed Cell (I. Cameron and T. B. Poole, eds.), Academic Press, New York, pp. 347–395.Google Scholar
  61. Gilmore, T., and Martin, G. S., 1983, Phorbol ester and diacylglycerol induce protein phosphorylation at tyrosine, Nature 294:771–773.Google Scholar
  62. Glenney, J., Glenney, P., and Weber, K., 1982, Erythroid spectrin, brain fodrin, and intestinal brush border protein (TW-260/240) are related molecules containing a common calmodulinbinding subunit bound to a variant cell type-specific subunit, Proc. Natl. Acad. Sci. USA 79:4002.PubMedGoogle Scholar
  63. Gospodarowicz, D., and Moran, J. S., 1976, Growth factors in mammalian cell culture, Annu. Rev. Biochem. 45:531–558.PubMedGoogle Scholar
  64. Gottesman, M. M., Singh, T., LeCarn, A., Roth, C, Nicholas, J. C, Cabral, F., and Pastan, I., 1980, Cyclic-AMP-dependent phosphorylation in cultured fibroblasts: A genetic approach, Cold Spring Harbor Conf. Cell Prolif. 8:195–209.Google Scholar
  65. Green, H., 1978, Cyclic AMP in relation to proliferation of the epidermal. A new view, Cell 15:801– 811.PubMedGoogle Scholar
  66. Grotendorst, G., 1984, Alteration of the chemotactic response of NIH/3T3 cells to PDGF by growth factors, transformation, and tumor promotors, Cell 36:279–285.Google Scholar
  67. Grotendorst, G., Seppä, H., Kleinman, H., and Martin, G., 1981, Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor, Proc. Natl. Acad. Sci. USA 78:3669–3672.PubMedGoogle Scholar
  68. Grotendorst, G., Chang, T., Seppä, H., Kleinman, J., and Martin, G., 1982, Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells, J. Cell Physiol. 113:261–266.PubMedGoogle Scholar
  69. Guidotti, A., Hanbauer, I., and Costa, E., 1977, Nuclear translocation of catolytic subunits of cytosol cAMP-dependent protein kinase in the transgraphic induction of medullary tyrosine hydroxylase, Adv. Cyclic Nucleotide Res. 9:185–194.Google Scholar
  70. Habenicht, A. J. R., Glomset, J. A., King, W. C., Nist, C., Mitchell, C. D., and Ross, R., 1981, Early changes in phosphatidylinositol and arachidonic acid metabolism in quiescent Swiss 3T3 cells stimulated to divide by platelet-derived growth factor, J. Biol. Chem. 256:12329–12335.PubMedGoogle Scholar
  71. Haigler, H. T., McKenna, J. A., and Cohen, S., 1979, Rapid stimulation of pinocytosis inhuman carcinoma cells A-431 by epidermal growth factor, J. Cell Biol. 83:82–90.PubMedGoogle Scholar
  72. Hathaway, D. R., and Adelstein, R. S., 1979, Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity, Proc. Natl. Acad. USA 76:1653–1657.Google Scholar
  73. Hazelton, B., Mitchell, B., and Tupper, J., 1979, Calcium, magnesium, and growth control in the WI-38 human fibroblast cell, J. Cell Biol. 83:487–498.PubMedGoogle Scholar
  74. Heldin, C. H., and Westermark, B., 1984, Growth factors: Mechanism of action and relation to oncogenes, Cell 37:19–20.Google Scholar
  75. Heldin, C. H., Westermark, B., and Wasteson, A., 1981, Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia, Proc. Natl. Acad. Sci. USA 78:3664–3668.PubMedGoogle Scholar
  76. Heldin, C. H., Westeson, A., and Westermark, B., 1985, Platelet-derived growth factor, Mol. Cell. Endocrinol. 39:169–187.PubMedGoogle Scholar
  77. Herman, B., and Pledger, W., 1985, Platelet-derived growth factor-induced alterations in vinculin and actin distribution in BALB/c-33 cells, J. Cell Biol. 100:1031–1040.PubMedGoogle Scholar
  78. Herman, B., Harrington, M., Olashaw, N., and Pledger, W., 1986, Identification of the cellular mechanisms responsible for platelet-derived growth factor induced alterations in cytoplasmic vinculin distribution, J. Cell. Physiol. 126:115–125.PubMedGoogle Scholar
  79. Herman, I., Crisona, N., and Pollard, T., 1981, Relation between cell activity and distribution of cytoplasmic actin and myosin, J. Cell Biol. 90:84–91.PubMedGoogle Scholar
  80. Hesketh, T. R., Smith G. A., and Metcalfe, J. C, 1982, Calcium and lymphocyte activation, in: Ions, Cell Proliferation, and Cancer (A. L. Boynton, W. L. McKeehan and J. F. Whitfield, eds.), Academic press, New York, pp. 397–415.Google Scholar
  81. Hesketh, T. R., Smith, G. A., Moore, J. P., Taylor, M. V., and Metcalfe, J. C, 1984, Free cytoplasmic calcium concentration and the mitogenic stimulation of lymphocytes, J. Biol. Chem. 258:4876–4882.Google Scholar
  82. Hesketh, T. R., Moore, J. P., Morris, J. D. H., Taylor, M. V., Rogers, J., Smith, G. A., and Metcalfe, J. C., 1985, A common sequence of calcium of pH signals in the mitogenic stimulation of eukaryatic cells, Nature 313:481–484.PubMedGoogle Scholar
  83. Highfield, D. P., and Dewey, W. C, 1972, Inhibition of DNA synthesis by synchronized Chinese hamster ovary cells treated in Gl or early S phase with cytohexamide or puromycin, Exp. Cell Res. 75:314–320.PubMedGoogle Scholar
  84. Hoffman, R., Ristow, H.-J., Packowsky, H., and Frank, W., 1974, Phospholipid metabolism in embryonic rat fibroblasts following stimulation by a combination of the serum proteins SI and S2, Eur. J. Biochem. 49:317–324.Google Scholar
  85. Hokin, L. E., 1985, Receptors and phosphoinositide-generated second messengers, Annu. Rev. Biochem. 54:205–235.PubMedGoogle Scholar
  86. Hollenberg, M. D., and Cautrecasas, P., 1973, Epidermal growth factor: Receptors in human fibroblasts and modulation of action by cholera toxin, Proc. Natl. Acad. Sci. USA. 70:2964–2968.PubMedGoogle Scholar
  87. Hsei, A., and Puck, T., 1971, Morphological transformation of Chinese hamster cells by dibutyryl andenosine cyclic 3‘:5’monophosphate and testosterone, Proc. Natl. Acad. Sci. USA 68:358–361.Google Scholar
  88. Huang, J. S., Huang, S. S., Kennedy, B., and Devel, T. F., 1982, Platelet-derived growth factor: Specific binding to target cells, J. Biol. Chem. 257:8130–8136.PubMedGoogle Scholar
  89. Hunter, T., 1985, Oncogenes and growth control, Trends Biochem. Sci. 10:275–280.Google Scholar
  90. Hunter, T., and Cooper, J. A., 1981, Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells, Cell 24:741–752.PubMedGoogle Scholar
  91. Hunter, T., Ling, N., and Cooper, J. A., 1984, Protein kinase C phosphorylationof the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane, Nature 311:480–483.PubMedGoogle Scholar
  92. Iwashita, S., Fox, C. F., 1984, Epidermal growth factor and potent phorbol tumor promoters induce epidermal growth factor receptor phosphorylation in a similar but distinctly different manner in human epidermoid carcinoma A431 cells, J. Biol. Chem. 259:2559–2567.PubMedGoogle Scholar
  93. Jackson, P., and Bellet, A., 1985, Reduced microfilament organization in adenovirus type 5-infected rat embryo cells; A function of early region la, J, Virol, 55:644-650. Jacobsen, K., Elson, E., Koppel, D., Webb, W., 1983, International workshop on the application of fluorescence photobleaching techniques to problems in cell biology, Fed. Proc. 42: 72–79.Google Scholar
  94. Jacobsen, K., Elson, E., Koppel, D., Webb, W., 1983, International workshop on the application of fluorescence photobleaching techniques to problems in cell biology, Fed. Proc. 42: 72–79.Google Scholar
  95. Janmey, P., Chaponnier, C., Lind, S., Zaner, K., Stossel, T., and Yin, H., 1985, Interactions of gelsolin and gelsolin-actin complexes with actin. Effects of calcium on actin nucleation, filament severing, and end blocking, Biochemistry 24:3714–3723.Google Scholar
  96. Johnson, P. C, Ware, J. A., Clivedon, P. B., Smith, M., Dvorak, A. M., and Salzman, E. W., 1985, Measurement of ionized calcium in blood platelets with the photoprotein aequorin, J. Biol. Chem. 260:2069–2076.PubMedGoogle Scholar
  97. Kaever, V., and Resch, K., 1985, Are cyclic nucleotides involved in the initiation of mitogenic activation of human lymphocytes?, Biochem. Biophys. Acta 846:216–225.PubMedGoogle Scholar
  98. Kaibuchi, K., Takai, Y., and Nishizuka, Y., 1981, Cooperative roles of various membrane phospholipids in the activation of calcium-activated, phospholipid-dependent protein kinase, J. Biol. Chem. 256:7146–7149.PubMedGoogle Scholar
  99. Kakiuchi, R., Inui, M., Morimoto, K., Kanda, K., Sobue, K., and Kakiuchi, S., 1983, Caldesmon, a calmodulin-binding, F-actin-interacting protein, is present in aorta, uterus, and platelets, FEBSLett. 154:351–356.Google Scholar
  100. Kamine, J., and Rubin, H., 1976 , Magnesium required for serum stimulation of growth in cultures of chick embryo fibroblasts, Nature 263:143–145.PubMedGoogle Scholar
  101. Keith, C., DiPaola, M., Maxfield, F., and Shelanski, M., 1983, Microinjection of Ca2+-calmodulin causes a localized depolymerization of microtubules, J. Cell Biol. 97:1918–1924.PubMedGoogle Scholar
  102. Kelly, K., Cochran, B. H., Stiles, C. D., and Leder, P., 1983, Cell-specific regulation of the cmyc gene by lymphocyte mitogens and platelet-derived growth factor, Cell 35:603–610.PubMedGoogle Scholar
  103. Kikkawa, U., Takai, Y., Tanaka, Y., Miyake, R., and Nishizuka, Y., 1983, Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters, J. Biol. Chem. 258:11442–11445.PubMedGoogle Scholar
  104. Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U., Nishizuka, Y., 1980, Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidy- linositol turnover, J. Biol. Chem. 255:2273–2276.Google Scholar
  105. Krupp, M. N., Connolly, D. T., and Lane, M. D., 1982, Synthesis, turnover, and down regulation of epidermal growth factor receptors in human A431 epidermoid carcinoma cells and skin fibroblasts, J. Biol. Chem. 257:11489–11496.PubMedGoogle Scholar
  106. L’Allemain, G., Franchi, A., Cragoe, E. J., Jr., and Pouyssegur, J., 1984a, Blockade of the Na+/H+ antiport abolishes growth factor-induced DNA synthesis in fibroblasts. Structure-activity relationships in the amiloride series, J. Biol. Chem. 259:4313–4319.PubMedGoogle Scholar
  107. L’Allemain, G., Paris, S., Pouyssegur, J., 1984b, Growth factor action and intracellular pH regulation in fibroblasts, J. Biol. Chem. 259:5809–5815.PubMedGoogle Scholar
  108. L’Allemain, G., Paris, S., and Pouyssegur, J., 1985, Role of a Na-dependent Cl-/HCO3 e-change in regulation of intracellular pH in fibroblasts, J. Cell Biol. 260:4877–4883.Google Scholar
  109. Lang, V., Pryhitka, C., and Buckley, J. T., 1977, Effect on neomycin and ionophore A23187 and ATP levels and turnover of polyphosphoinositides in human erythrocytes, Can. J. Biochem. 55:1007–1012.PubMedGoogle Scholar
  110. Lassing, I., and Lindberg, V., 1985, Specific interaction between phosphatidylinositol 4,5-biphos- phate and profilactin, Nature 314:472–474.PubMedGoogle Scholar
  111. Lawrence, T., Ginzberg, R., Gilula, N., Beers, W., 1979, Hormonally induced cell shape changes in cultured rat ovarian granulosa cells, J. Cell Biol. 80:21–36.PubMedGoogle Scholar
  112. Leach, K., James, M., and Blumberg, P., 1983, Characterization of a specific phorbol ester aporeceptor in mouse brain cytosol, Proc. Natl. Acad. Sci. USA 80:4208–4212.PubMedGoogle Scholar
  113. Lee, L. S., and Weinstein, I. B., 1978, Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors, Science 202:313–315.PubMedGoogle Scholar
  114. Leof, E. B., Wharton, N., O’Keefe, E., and Pledger, W. J., 1982, Elevated intracellular concentrations of cyclic AMP inhibited serum-stimulated, density arrested Balb/c-3T3 cells in mid Gl, J. Cell. Biochem. 19:93–103.Google Scholar
  115. Lin, C. R., Chen, W. S., Lazar, C. S., Carpenter, C. D., Gill, G. N., Evans, R. M., and Rosenfeld, M. G., 1986, Protein kinase C phosphorylation at the 654 of the unoccupied EGF receptor and EGF binding regulate functional receptor loss by independent mechanisms, Cell 44:839–848.PubMedGoogle Scholar
  116. Lodhi, S., Weiner, N. D., and Schacht, J., 1979, Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids, Biochem. Biophys. Acta 557:1–8.PubMedGoogle Scholar
  117. Luby-Phelps, K., Taylor, D., and Lanni, F., 1986, Probing the structure of cytoplasm, J. Cell Biol. 102:2015–2022.PubMedGoogle Scholar
  118. Maclntyre, D. E., and Drummond, A. H., 1985, Tumour-promoting phorbol esters inhibit agonistinduced phosphotidate formation and Ca2+ flux in human platelets, FEBS Lett. 180:160–164.Google Scholar
  119. Majerus, P. W., Newfeld, E. J., and Wilson, D. B., 1984, Production of phosphoinositide-derived messengers, Cell 37:701–703.PubMedGoogle Scholar
  120. Malm, B., Persson, T., and Lindberg, U., 1981, Characterization of platelet extracts before and after stimulation with respect to the possible role of profilactin as microfilament precursor, Cell 23:145–153.Google Scholar
  121. Manalan, A., and Klee, C., 1984, Calmodulin, Adv. Cyclic Nucleotide Protein Phosphorylation Res. 18:227–279.PubMedGoogle Scholar
  122. Maness, P., 1981, Actin structure in fibroblasts: Its possible role in transformation and tumoregenesis, Cell Muscle Motil. 1:335–373.Google Scholar
  123. Marceau, N., and Swierenga, S., 1985, Cytoskeletal events during Ca2+- or EGF-induced initiation of DNA synthesis in cultured cells, in: Cell Muscle Motility ,Vol. 6 (J. Shay, ed.), Plenum Press, New York, pp. 97–140.Google Scholar
  124. Marcum, J., Dedman, J., Brankley, B., and Means, A., 1978, Control of microtubule assemblydisassembly by calcium-dependent regulator protein, Proc. Natl. Acad. Sci. USA 75:3771– 3775.PubMedGoogle Scholar
  125. Markey, F., Larsson, H., Weber, K., and Lindberg, U., 1982, Nucleation of actin polymerization from profilactin opposite effects of different nuclei, Biochem. Biophys. Acta 704:43–51.PubMedGoogle Scholar
  126. McKeehan, W. L., and McKeehan, K. A., 1980, Serum factors modify the cellular requirement for Ca2+, K+, Mg2+, phosphate ions, and 2-oxocarboxylic acids for multiplication of normal human fibroblasts, Proc. Natl. Acad. Sci. USA 77:3417–3421.PubMedGoogle Scholar
  127. McKeehan, W. L., McKeehan, K. A., and Calkins, D., 1982, Epidermal growth factor modifies Ca2+, Mg2+, and 2-oxocarboxylic acid, but not K+ and phosphate ion requirement for multiplication of human fibroblasts, Exp. Cell Res. 140:25–30.PubMedGoogle Scholar
  128. McNeil, P. L., McKenna, M. D., and Taylor, D. L., 1985, A transient rise in cytosolic calcium follows stimulation of quiescent cells with growth factors and is inhibitable with phorbol myristate acetate, J. Cell Biol. 101:372–379.PubMedGoogle Scholar
  129. Means, A., Tash, J., Chafouleas, J., Legace, L., and Guerriero, V., 1982, Regulation of the cytoskeleton by Ca2+-calmodulin and cAMP, Ann. N.Y. Acad. Sci. 383:69–84.PubMedGoogle Scholar
  130. Meigs, J., and Wang, Y.-L., 1986, Reorganization of alpha-actinin and vinculin induced by a phorbol ester in living cells, J. Cell Biol. 102:1430–1438.PubMedGoogle Scholar
  131. Mellstrom, K., Hoglung, A., Nister, M., Heldin, C., Westermark, B., and Lindberg, U., 1983, The effect of platelet-derived growth factor on morphology and motility of human glial cells, J. Muscle Res. Cell. Motil. 4:589–609.Google Scholar
  132. Michell, R. H., 1975, Inositol phospholipids and cell surface receptor function, Biochem. Biophys. Acta. 415:81–147.PubMedGoogle Scholar
  133. Miller, S., Wolf, A., and Amaud, C, 1976, Bone cells in culture: Morphologic transformation by hormones, Science 192:1340–1343.PubMedGoogle Scholar
  134. Mittal, A., and Bereiter-Hahn, J., 1985, Ionic control of locomotion and shape of epithelial cells: 1. Role of calcium influx, Cell Motil. 5:123–136.PubMedGoogle Scholar
  135. Moolenaar, W. H., Kruijer, W., Tilly, B. C., Verlaan, I., Bierman, A. J., and de Lat, S. W., 1986, Growth factor-like action of phosphatidic acid, Nature 323:171–173.PubMedGoogle Scholar
  136. Moolenaar, W. H., Tsien, R. Y., van der Saag, P. T., and de Laat, S. W., 1983, Na+/H+ exchange and cytoplasmic pH in the action of growth factors in human fibroblasts, Nature 304: 645–648.PubMedGoogle Scholar
  137. Moolenaar, W. H., Tertoolen, L. G. J., de Laat, S. W., 1984a, Phorbol ester and diacylglycerol mimic growth factors in raising cytoplasmic pH, Nature 312:371–376.PubMedGoogle Scholar
  138. Moolenaar, W. H., Tertoolen, L. G. J., and de Lat, S. W., 1984b, Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts, J. Biol. Chem. 259:8066–8069.PubMedGoogle Scholar
  139. Morris, J. D. H., Metcalfe, J. C., Smith, G. A., Heskieth, T. R., and Taylor, M. V., 1984, Some mitogens cause rapid increases in free calcium in fibroblasts, FEBS Lett. 169:189–193.PubMedGoogle Scholar
  140. Mroczkoski, R., Mosig, G., and Cohen, S., 1984, ATP-stimulated interaction between epidermal growth factor and super-coiled DNA, Nature 309:270–273.Google Scholar
  141. Naccache, P. H., Molski, T. F. P., Borgeat, P., White, J. R., and Shaafi, R. I., 1985, Phorbol esters inhibit the fMet-Leu-Phe- and leukotrinene B4 stimulated calcium mobilization and enzyme secretion in rabbit neutrophils, J. Biol. Chem. 260:2125–2131.PubMedGoogle Scholar
  142. Naka, M., Nishikawa, M., Adelstein, R., and Hidaka, H., 1983, Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains, Nature 306:490–492.PubMedGoogle Scholar
  143. Nakamura, K. D., Martinez, R., and Weber, M. J., 1983, Tyrosine phosphorylation of specific proteins after mitogen stimulation of chicken embryo fibroblasts, Mol. Cell. Biol. 3:380–390.PubMedGoogle Scholar
  144. Nicholson, N. B., Chen, S., Blank, G., and Pollack, R., 1984, SV40 transformation of Swiss 3T3 cells can cause a stable reduction in the calcium requirement for growth, J. Cell Biol. 99:2314–2321.PubMedGoogle Scholar
  145. Niedel, J., Kuhn, L., and Vanderbank, G., 1983, Phorbol diester receptor copurifies with protein kinase C, Proc. Natl. Acad. Sci. USA 80:36–40.PubMedGoogle Scholar
  146. Nilsson, J., Thyberg, J., Heldin, C. H., Westermark, B., and Wasteson, A., 1983, Surface binding and internalization of platelet-derived growth factor in human fibroblasts, J. Biol. Chem. 80:5592– 5596.Google Scholar
  147. Nishimura, J., and Deuel, T. F., 1981, Stimulation of protein phosphorylation in Swiss mouse 3T3 cells by platelet-derived growth factor, Biochem. Biophys. Res. Commun. 103:355–361.PubMedGoogle Scholar
  148. Nishimura, J., Huang, J. S., and Deuel, T. F., 1982, Platelet-derived growth factor stimulates tyrosine-specific protein kinase activity in Swiss 3T3 cells membranes, Proc. Natl. Acad. Sci. USA 79:4303–4307.PubMedGoogle Scholar
  149. Nishizuka, Y., 1983, Phospholipid turnover and cyclic nucleotides in hormone research, in: Evolution of Hormone-Receptor Systems ,Alan R. Liss, New York, pp. 425–439.Google Scholar
  150. Nishizuka, Y., 1984, The role of protein kinase C in cell surface signal transduction and tumour production, Nature 308:693–698.PubMedGoogle Scholar
  151. Ojakian, G., 1981, Tumor promotor-induced changes in the permeability of epithelial cell tight junctions, Cell 23:95–103.PubMedGoogle Scholar
  152. Olashaw, N. E., O’Keefe, E. J., and Pledger, W. J., 1986, Platelet-derived growth factor modulates epidermal growth factor receptors by a mechanism distinct from that of phorbol esters, Proc. Natl. Acad. Sci. USA 83:3834–3838.PubMedGoogle Scholar
  153. Olsnes, S., Tonnessen, T., and Sanding, K., 1986, pH-regulated anion antiport in nucleated mammalian cells, J. Cell Biol. 102:967–971.PubMedGoogle Scholar
  154. O’Neill, C, Riddle, P., and Rozengurt, E., 1985, Stimulating the proliferation of quiescent 3T3 fibroblasts by peptide growth factors or by agents which elevate cellular cAMP level has opposite effects on motility, Exp. Cell Res. 156:65–78.PubMedGoogle Scholar
  155. Orellana, S. A., Solski, P. A., and Brown, J. H., 1985, Phorbol ester inhibits phosphoinositide hydrolysis and calcium mobilization in cultured astrocytoma cells, J. Biol. Chem. 260:5236– 5239.PubMedGoogle Scholar
  156. Owen, N. E., and Villereal, M. L., 1982, Evidence for a role of calmodulin in serum stimulation of Na+ influx in human fibroblasts, Proc. Natl. Acad. Sci. USA 79:3537–3541.PubMedGoogle Scholar
  157. Pardee, A. B., Dubrow, R., Hamlin, J. L., and Kletzeen, R. F., 1978, Animal cell cycle, Annu. Rev. Biochem. 47:715–750.PubMedGoogle Scholar
  158. Paris, S., and Rozengurt, E., 1982, Cyclic AMP stimulation of Na-K pump activity in quiescent Swiss 3T3 cells, J. Cell Physiol. 112:273–280.PubMedGoogle Scholar
  159. Pastan, I., and Johnson, G. S., 1974, Cyclic AMP and the transformation of fibroblasts, in: Advances in Cancer Research (G. Klein, S. Weinhouse and A. Haddow, eds.), Academic Press, New York, pp. 303–329.Google Scholar
  160. Pastan, I. H., Johnson, G. S., Anderson, W. B., 1975, Role of cyclic nucleotides in growth control, Annu. Rev. Biochem. 44:491–668.PubMedGoogle Scholar
  161. Pledger, W., Hart, C., Locatell, K., Scher, L., 1981, Platelet-derived growth factor-modulated proteins: Constitutive synthesis by a transformed cell line, Proc. Natl. Acad. Sci. USA 78:4358–4362.PubMedGoogle Scholar
  162. Pollack, R., Osborn, M., and Weber, K., 1975, Patterns of organization of actin and myosin in normal and transformed cultured cells, Proc. Natl. Acad. Sci. USA 72:994–998.PubMedGoogle Scholar
  163. Pouyssegur, J., Sardet, C., Franchi, A., L’Allemain, G., and Paris, S., 1984, A specific mutation abolishing Na+/H+ antiport activity in hamster fibroblast precludes growth at neutral and aridic pH, Proc. Natl. Acad. Sci. USA 81:4833–4837.PubMedGoogle Scholar
  164. Pouyssegur, J., Franchi, A., L’Allemain, G., and Paris, S., 1985, Cytoplasmic pH, a key determinant of growth factor-induced DNA synthesis in quiescent fibroblasts, Fed. Eur. Biochem. Soc. 190:115–119.Google Scholar
  165. Prentki, M., Biden, T. J., Janjic, D., Irvine, R. F., Berridge, M. J., and Wollheim, C. B., 1984, Rapid mobilization of Ca2+ from rat insulinima microsomes by inositol-l,4,5-triphosphate, Nature 309:562–564.Google Scholar
  166. Pruss, R. M., and Herschman, H. R., 1979, Cholera toxin stimulates division of 3T3 cells, J. Cell Physiol. 98:469–473.PubMedGoogle Scholar
  167. Puck, T., 1977, Cyclic AMP, the microtubule-microfilament system, and cancer, Proc. Natl. Acad. Sci. USA 74:4491–4495.PubMedGoogle Scholar
  168. Quigley, J., 1979, Phorbol ester induced morphological changes in transformed chick fibroblasts: Evidence for direct catalytic involvement of plasminogen activator, Cell 17:131–141.PubMedGoogle Scholar
  169. Rasmussen, H., 1980, Calcium and cAMP in stimulus-response coupling, Ann. N.Y. Acad. Sci. 356:346–353.PubMedGoogle Scholar
  170. Rasmussen, H., Koijima, I., Koijima, K., Zawalich, N., and Apfeldorf, W., 1984, Calcium as intracellular messenger: Sensitivity modulation, C-kinase pathway, and sustained cellular release, Adv. Cyclic Nucleotide Protein. Phosphorylation Res. 18:159–193.Google Scholar
  171. Rebhun, L., 1977, Cyclic nucleotides, calcium, and cell division, Int. Rev. Cytol. 49:1–54.Google Scholar
  172. Rifkin, D., Crowe, R., and Pollack, R., 1979, Tumor promoters induce changes in the chick embryo fibroblast cytoskeleton, Cell 18:361–368.PubMedGoogle Scholar
  173. Rink, T. J., and Hallam, T. J., 1984, What turns platelets on? Trends Biochem. Sci. 9:215–219.Google Scholar
  174. Ristow, H.-J., Frank, W., Frohlich, M., 1973, Stimulation of embryonic rat cells by calf serum. V. Metabolism of inositol and choline phospholipids. Z. Naturforsch. 28:188–194.Google Scholar
  175. Roos, A., and Boron, F., 1981, Intracellular pH, Physiol. Rev. 61:296–433.PubMedGoogle Scholar
  176. Rosenfeld, M. E., Bowen-Pope, D. F., and Ross, R., 1984, Platelet-derived growth factor-morphologic and biochemical studies of binding, internalization, and degradation, J. Cell Physiol. 121:263–274.Google Scholar
  177. Rosoff, P. M., and Cantley, L. C., 1985, Stimulation of the T3-T cell receptor-associated Ca2+ influx enhances the activity of the Na+/H+ exchanges in a leukemic human T cell line, J. Biol. Chem. 260:14053–14059.PubMedGoogle Scholar
  178. Ross, R., and Vogel, A., 1978, The platelet-derived growth factor, Cell 14:203–210.PubMedGoogle Scholar
  179. Ross, R., Raines, E. W., and Bowen-Pope, D. F., 1986, The biology of platelet-derived growth factor, Cell 46:155–169.PubMedGoogle Scholar
  180. Rossow, P. W., Riddle, V. G. H., and Pardee, A. B., 1979, Synthesis of labile serum dependent protein in early G1 controls animal cell growth, Proc. Natl. Acad. Sci. USA 76:4446–4450.PubMedGoogle Scholar
  181. Rothenberg, P., Glaser, L., Schlesinger, P., and Cassel, P., 1983, Activation of Na+/H+ exchange by epidermal growth factor elevates intracellular pH in A431 cells, J. Biol. Chem 258: 12644–12653.PubMedGoogle Scholar
  182. Rozengurt, E., 1981a, Stimulation of Na influx, Na-K pump activity, and DNA synthesis in quiescent cultured cells, Adv. Enzyme Regul. 19:61–85.Google Scholar
  183. Rozengurt, E., 1981b, Cyclic AMP: A growth-promoting signal for mouse 3T3 cells, Adv. Cyclic Nucleotide Res. 14:429–442.PubMedGoogle Scholar
  184. Rozengurt, E., 1982a, Monovalent ion fluxes, cyclic nucleotides, and the stimulation of DNA synthesis in quiescent cells, in: Ions, Cell Proliferation, and Cancer (A. L. Boynton, W. L. McKeehan, and J. F. Whitfield, eds.), Academic Press, New York, pp. 259–281.Google Scholar
  185. Rozengurt, E., 1982b, Synergistic stimulation of DNA synthesis by cyclic AMP derivatives and growth factors in mouse 3T3 cells, J. Cell Physiol. 112:243–250.PubMedGoogle Scholar
  186. Rozengurt, E., and Dicker, P., 1978, Stimulation of DNA synthesis by tumor promoter and pure mitogenic factors, Nature 276:723–726.PubMedGoogle Scholar
  187. Rozengurt, E., Legg, A., Strang, G., Courtenay-Luck, N., 1981, Cyclic AMP: A mitogenic signal for Swiss 3T3 cells, Proc. Natl. Acad. Sci. USA 78:4392–4396.PubMedGoogle Scholar
  188. Rozengurt, E., Stroobant, P., Waterfield, M. D., Deuel, T. F., and Keehan, M., 1983, Platelet-derived growth factor elicits cyclic AMP accumulation in Swiss 3T3 cells: Role of prostaglandin production, Cell 34:265–272.PubMedGoogle Scholar
  189. Rozengurt, E., Rodriguez-Pena, A., Coombs, M., and Sinnett-Smith, J., 1984, Diacylglycerol stimulated DNA synthesis and cell division in mouse 3T3 cells: Role of Ca2+ sensitive phos- pholipid-dependent protein kinase, Proc. Natl. Acad. Sci. USA 81:5748–5752.PubMedGoogle Scholar
  190. Rubin, H., 1971, pH and population density in the regulation of animal cell multiplication, J. Cell. Biol. 51:686–702.PubMedGoogle Scholar
  191. Ryback, S. M., and Stockdale, F. E., 1981, Growth effects of lithium chloride in Balb/c 3T3 fibroblasts and Madin-Darby canine kidney epithelial cells, Exp. Cell Res. 136:263–270.Google Scholar
  192. Sagi-Eisenberg, R., Lieman, H., and Pecht, S., 1985. Protein kinase C regulation of the receptor-coupled calcium signal in histamine-secreting rat basophilic cells, Nature 313:59–60.PubMedGoogle Scholar
  193. Salomon, P. S., 1981, Inhibition of epidermal growth factor binding to mouse embryonal carcinoma cells by phorbol esters mediated by specific phorbol ester receptors, J. Biol. Chem. 256:7958– 7966.PubMedGoogle Scholar
  194. Sawyer, S. T., and Cohen, S., 1981, Enhancement of calcium uptake and phosphatidylinositol turnover by epidermal growth factor in A-431 cells, Biochemistry 20:6280–6286.PubMedGoogle Scholar
  195. Scher, C. D., Shepard, R. C., Antoniades, H. N., and Stiles, C. D., 1979, Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycle, Biochem. Biophys. Acta 560:217–241.PubMedGoogle Scholar
  196. Schlessinger, J., and Geiger, B., 1981, Epidermal growth factor induces redistribution of actin and actinin in human epidermal carcinoma cells, Exp. Cell Res. 134:273–279.PubMedGoogle Scholar
  197. Schliwa, M., Nakamura, T., Porter, K. R., and Euteneur, U., 1984, A tumor promoter induces rapid and coordinated reorganization of actin and vinculin in cultured cells, J. Cell Biol. 99:1045–1059.PubMedGoogle Scholar
  198. Sefton, B. M., and Hunter, T., 1984, Tyrosine protein kinases, Adv. Cyclic Nucleotide Protein Phosphorylation Res. 18:195–225.PubMedGoogle Scholar
  199. Seppa, H. E. J., Grotendorst, G. R., Seppä, S. I., Schiffman, E., Martin, G. R., 1982, The platelet-derived growth factor is a chemoattractant for fibroblasts, J. Cell Biol. 92:584–588.PubMedGoogle Scholar
  200. Shoyab, M., De Larco, J. E., and Todaro, G. J., 1979, Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors, Nature 279:387–391.PubMedGoogle Scholar
  201. Sibley, D. R., and Lefkowitz, R. J., 1985, Molecular mechanisms of receptor desensitization using the α-adrenergic receptor-coupled adenylate cyclase system as a model, Nature 317:124–129.PubMedGoogle Scholar
  202. Silverstein, S., Steinman, R., and Cohn, Z., 1979, Endocytosis, Annu. Rev. Biochem. 46:669–722.Google Scholar
  203. Singh, T. J., Hochman, J., Verna, R., Chapman, M., Abraham, I., Pastan, I., and Gottesman, M. J., 1985, Characterization of a cyclic AMP-resistant Chinese hamster ovary cell mutant containing both wild-type and mutant species of type I regular subunit of cyclic AMP-dependent protein kinase, J. Biol. Chem. 260:13927–13933.PubMedGoogle Scholar
  204. Stiles, C. D., 1983, The molecular biology of platelet-derived growth factor, Cell 33:653.PubMedGoogle Scholar
  205. Stoscheck, C. M., and Carpenter, G., 1984, Down regulation of epidermal growth factor receptors: Direct demonstration of receptor degradation in human fibroblasts, J. Cell Biol. 98:1048–1053.PubMedGoogle Scholar
  206. Sutherland, E. W., 1972, Studies on the mechanisms of hormone action, Science 177:401–408.PubMedGoogle Scholar
  207. Taylor, D., and Condeelis, J., 1979, Cytoplasmic structure and contractibility in amoeboid cells, Int. Rev. Cytol. 56:57–144.PubMedGoogle Scholar
  208. Taylor, D. L., and Fecheimer, M., 1982, Cytoplasmic structure and contractility: the solationcontraction coupling hypothesis, Philos. Trans. R. Soc. Lond. [Biol.] 299:185–197.Google Scholar
  209. Taylor, D., and Wang, Y.-L., 1980, Fluorescently labelled molecules as probes of the structure and function of living cells, Nature 284:405–410.PubMedGoogle Scholar
  210. Taylor, D., Wang, Y.-L., and Heiple, J., 1980, The contractile basis of amoeboid movement. VII. The distribution of fluorescently labeled actin in living amebas, J. Cell Biol. 86:590–598PubMedGoogle Scholar
  211. Taylor, D., Amato, P., McNeil, P., Luby-Phelps, K., and Tanasugarn, L., 1986, Spatial and temporal dynamics of specific molecules and ions in living cells, in: Applications of Fluorescence in the Biomedical Sciences (D. Taylor, A. Waggoner, R. Murphy, F. Lanni, and R. Birge, eds.), Alan R. Liss, New York, pp. 347–376.Google Scholar
  212. Thyberg, J., 1984, The microtubular cytoskeleton and the initiation of DNA synthesis, Exp. Cell. Res. 155:1–8.PubMedGoogle Scholar
  213. Tilney, L., 1975, Actin filaments in the acrosomal reaction of Limulus sperm, J. Cell Biol. 64:289– 310.PubMedGoogle Scholar
  214. Tsien, R. Y., Pozzan, T., and Rink, T. J., 1982, T-cell mitogens cause early changes in cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator, J. Cell Biol. 94:325–334.Google Scholar
  215. Tsuda, T., Kaibuchi, K., West, B., and Takai, Y., 1985, Involvement of Ca2+ in platelet-derived growth factor-induced expression of c-myc oncogene in Swiss 3T3 fibroblasts, Fed. Eur. Biochem. Soc. 187:43–46.Google Scholar
  216. Ushiro, H., and Cohen, S., 1980, Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes, J. Biol. Chem. 255:8363–8365.PubMedGoogle Scholar
  217. Vicentini, L. M., and Villereal, M. L., 1985, Activation of Na+/H+ exchange in cultured fibroblasts: Synergism and antagonism between phorbol ester, Ca2+ ionophore, and growth factors, Proc. Natl. Acad. Sci. USA 82:8053–8056.Google Scholar
  218. Waggoner, A., 1986, Fluorescent probes for analysis of cell structure, function, and health by flow and image cytometry, in: Applications of Fluorescence in the Biomedical Sciences (D. Taylor, A. Waggoner, R. Murphy, F. Lanni, and R. Birge, eds.), Alan R. Liss, New York, pp. 3– 28.Google Scholar
  219. Wang, E., and Goldberg, A., 1976, Changes in microfilament organization and surface topography upon transformation of chick embryo fibroblasts with Rous sarcoma virus, Proc. Natl. Acad. Sci. USA 73:4065–4069.PubMedGoogle Scholar
  220. Wang, Y.-L., 1985, Exchange of actin subunits at the leading edge of living fibroblasts; possible role of treadmilling, J. Cell Biol. 101:597–602.PubMedGoogle Scholar
  221. Watson, S. P., and Lapetina, E. G., 1985, 1,2-diacylglycerol and phorbol ester inhibit agonistinduced formation of inositol phosphates in human platelets: Possible implications for negative feedback regulation of inositol phospholipid hydrolysis, Proc. Natl. Acad. Sci. USA 82:2623–2626.PubMedGoogle Scholar
  222. Werth, D., and Pastan, I., 1984, Vinculin phosphorylation in response to calcium and phorbol esters in intact cells, J. Biol. Chem. 259:5264–5270.PubMedGoogle Scholar
  223. Wharton, W., Leof, E. B., Olashaw, N., Earp, H. S., and Pledger, W. J., 1982, Increases in cyclic AMP potentiate competence formation in Balb/C-3T3 cells, J. Cell. Physiol. 111:201–206.PubMedGoogle Scholar
  224. Whitaker, M. J., and Steinhardt, R. A., 1982, Ionic regulation of egg activation, Q. Rev. Biophys. 15:593–666.PubMedGoogle Scholar
  225. White, J. R., Huang, L. K., Hill, J., Naccache, P. H., Becker, E. L., and Shaafi, R. I., 1984, Effect of phorbol 12-myristate 13-acetate and its analogue 4,-phorbol 12, 13-didecanoate on protein phosphorylation and lysosomal enzyme release in rabbit neutrophils, J. Biol. Chem. 259:8605–8611.PubMedGoogle Scholar
  226. Whitely, B., Cassel, D., Zuang, U., and Glaser, L., 1984, Tumor promoter phorbol 12-myristate acetate inhibits mitogen-stimulated Na+/H+ exchange in human epidermal carcinoma A431 cells, J. Cell Biol. 99:1162–1166.Google Scholar
  227. Whitely, B., Duel, T., and Glaser, L., 1985, Modulation of the activity of the platelet-derived growth factor receptor by phorbol myristate acetate, Biochem. Biophys. Res. Commun. 129:854–861.Google Scholar
  228. Whitfield, J. F., 1982, The roles of calcium and magnesium in cell proliferation: An overview, in: Ions, Cell Proliferation, and Cancer (A. L. Boynton, W. L. McKeehan, and J. F., Whitfield, eds.), Academic Press, New York, pp. 283–294.Google Scholar
  229. Whitfield, J. F., MacManus, J. P., and Gillan, D. J., 1970, The possible mediation by cyclic AMP of the stimulation of thymocyte proliferation by vassopressin and the inhibition of this mitogenic action by throcalcitonin, J. Cell Physiol. 76:65–76.PubMedGoogle Scholar
  230. Whitfield, J. F., MacManus, J. P., Rixon, R. H., Boynton, A. L., Youdale, T., and Swierenga, S. H. H., 1976, The positive control of cell proliferation by the interplay of calcium ions and cyclic nucleotides-A review, In Vitro 12:1–18.PubMedGoogle Scholar
  231. Willingham, M., 1976, Cyclic AMP and cell behavior in cultured cells, Int. Rev. Cytol. 44:319–363.PubMedGoogle Scholar
  232. Willingham, M., and Pastan, I., 1975, Cyclic AMP and cell morphology in cultured fibroblasts, J. Cell Biol. 67:146–159.PubMedGoogle Scholar
  233. Zetterberg, A., and Engstrom, W., 1981, Mitogenic effect of alkaline pH on quiescent, serum-starved cells, Proc. Natl. Acad. Sci. USA 78:4334–4338.PubMedGoogle Scholar
  234. Zetterberg, A. W., and Larsson, O., 1985, Kinetic analysis of regulatory events in Gl leading to proliferation or quiescence of Swiss 3T3 cells, Proc. Natl. Acad. Sci. USA 82:5365–5369.PubMedGoogle Scholar
  235. Zigmond, S., 1982, Polymorphonuclear leukocyte response to chemotactic gradients, in: Cell Be havior (R. Bellaris, A. Curtis, and G. Dunn, eds.), Cambridge University Press, London, p. 183.Google Scholar
  236. Zigmond, S., and Hirsch, J., 1973, Leukocyte locomotion and chemotaxis: New methods for evaluation and demonstration of cell-derived chemotactic factor, J. Exp. Med. 137:387–400.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Paul L. McNeil
    • 1
  • D. Lansing Taylor
    • 1
  1. 1.Department of Biological Sciences and Center for Fluorescence Research in Biomedical SciencesCarnegie-Mellon UniversityPittsburghUSA

Personalised recommendations