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Signal Transduction in Proliferating Normal and Transformed Cells

  • M. J. O. Wakelam
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 94 / 2)

Abstract

The understanding of the early events induced in cells by growth factors has been facilitated by the use of cloned cell lines that can be made quiescent by either withdrawing serum growth factors from the culture medium or by allowing the cells to grow until the available growth factors are depleted and the cells are contact-inhibited. Removal of growth factors from an exponentially growing culture does not, however, stop proliferation immediately. Those cells in or beyond late G 1, and thus committed to division, complete the cell cycle (Zetterberg and Larsson 1985). When the resulting progeny cells and the other cells in the culture enter early G1, they progress no further. The production of mRNA in these arrested cells then falls, whilst the rate of degeneration of mRNA is unchanged (Rudland et al. 1975). The cultured cells are then said to be quiescent or G0 cells; for further discussion of this transition see Whitfield et al. (1987). Following the addition of serum or defined growth factors, the quiescent cells are stimulated to enter the cell cycle. Using this experimental system, the early biochemical events occurring in the cell in response to growth stimulation can be investigated. Such studies have demonstrated several types of early change including alterations in intracellular ion concentrations, protein phosphorylation and production of second messengers.

Keywords

Inositol Phosphate Inositol Trisphosphate Oncogene Product Inositol Phospholipid Type Beta Transform Growth Factor 
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.

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References

  1. Altman J (1988) Ins and outs of cell signalling. Nature 331:119–120PubMedGoogle Scholar
  2. Anzano MA, Roberts AB, De Larco JE, Wakefield LM, Assoian RK, Roche NS, Smith JM, Lazarus JE, Sporn MB (1985) Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. Mol Cell Biol 5:242–247PubMedGoogle Scholar
  3. Barbacid M (1987) ras genes. Ann Rev Biochem 56:779–827PubMedGoogle Scholar
  4. Berridge MJ (1987) Inositol lipids and cell proliferation. Biochim Biophys Acta 907:33–45PubMedGoogle Scholar
  5. Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 213:315–321Google Scholar
  6. Berridge MJ, Heslop JP, Irvine RF, Brown KD (1984) Inositol trisphosphate formation and calcium mobilisation in Swiss 3T3 cells in response to platelet-derived growth factor. Biochem J 222:195–201PubMedGoogle Scholar
  7. Besterman JM, Duronio V, Cuatrecasas P (1986) Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger. Proc Natl Acad SciUSA 83:6785–6789Google Scholar
  8. Betsholtz C, Johnsson A, Heldin C-H, Westermark B (1986) Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor-induced mitogenesis by suramin. Proc Natl Acad Sci USA 83:6440–6444PubMedGoogle Scholar
  9. Blac FM, Wakelam MJO (1989) Dosensitization A prostaglandin F2a stimulated inositol phosphate generation in NIH-3T3 fibroblasts transformed by overexpression of normal c-Ha-ras, c-Ki-ras and c-N-ras genes. Biochem J (in press)Google Scholar
  10. Bowen-Pope DF, Vogel A, Ross R (1984) Production of platelet-derived growth factorlike molecules and reduced expression of platelet-derived growth factor receptors ac-company transforming by a wide spectrum of agents. Proc Natl Acad Sci USA 81:2396–2400PubMedGoogle Scholar
  11. Brown KD, Blay J, Irvine RF, Heslop JP, Berridge MJ (1984) Reduction of epidermal growth factor receptor affinity by heterologous ligands: evidence for a mechanism involving the breakdown of phosphoinositides and the activation of protein kinase C. Biochem Biophys Res Commun 123:377–384PubMedGoogle Scholar
  12. Burger MM, Bombik BM, Breckenridge B McL, Shepphard JR (1972) Growth control and cyclic alterations of cyclic AMP in the cell cycle. Nature New Biol 239:161–162Google Scholar
  13. Cales C, Hancock JF, Marshall CJ, Hall A (1988) The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product. Nature 332:548–551PubMedGoogle Scholar
  14. Casey PJ, Gilman AG (1988) G protein involvement in receptor effector coupling. J Biol Chem 263:2577–2580PubMedGoogle Scholar
  15. Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkaw U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid dependent protein kinase by tumour- promoting phorbol esters. J Biol Chem 257:7847–7851PubMedGoogle Scholar
  16. Chiarrugi VP, Pasquali F, Vannucchi S, Ruggiero M (1986) Point mutated p2Vas couples a muscarinic receptor to calcium channels and polyphosphoinositide hydrolysis. Biochem Biophys Res Commun 141:591–599Google Scholar
  17. Cobbold PH, Rink TJ (1987) Fluorescence and bioluminescence measurement of cytoplasmic free calcium. Biochem J 248:313–328PubMedGoogle Scholar
  18. Cocco L, Gilmour RS, Ognibene A, Letcher A, Manzoli FA, Irvine RF (1987) Synthesis of polyphosphoinositides in nuclei of Friend cells. Biochem J 248:765–770PubMedGoogle Scholar
  19. Cockroft S (1987) Polyphosphoinositide phosphodiesterase: regulation by a novel guanine nucleotide binding protein, Gp. Trends Biochem Sci 12:75–78Google Scholar
  20. Connolly TM, Lawing WJ Jr, Majerus PW (1986) Protein kinase C phosphorylates human platelet inositol triphosphate 5’-monophosphatase, increasing phosphatase activity. Cell 46:951–958PubMedGoogle Scholar
  21. Corbin JD, Keely SL, Park CR (1975) The distribution and dissociation of cyclic adenosine 3’:5’-monophosphate-dependent protein kinases in adipose, cardiac and other tissues. J Biol Chem 250:218–225PubMedGoogle Scholar
  22. Costa M, Gerner EW, Russell DH (1976) Gx specific increases in cyclic AMP levels and protein kinase activity in Chinese hamster ovary cells. Biochim Biophys Acta 425:246–255PubMedGoogle Scholar
  23. Courtneidge S, Heber A (1987) An 81 kd protein complexed with middle T antigen and pp60c“src: a possible phosphatidylinositol kinase. Cell 50:1031–1037PubMedGoogle Scholar
  24. Cuttitta F, Carney DN, Mulshine J, Moody TW, Fedorki J, Fischler A, Minna JD (1985) Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316:823–826PubMedGoogle Scholar
  25. Delarco JE, Preston YA, Todaro GJ (1981) Properties of a sarcoma-growth-factor-like peptide from cells transformed by a temperature sensitive sarcoma virus. J Cell Physiol 109:143–152Google Scholar
  26. Doolittle RF, Hunkapiller MW, Hood LH, Devare SG, Robbins KC, Aaronson SA, Antoniades HN (1983) Simian sarcoma virus oncogene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275–280PubMedGoogle Scholar
  27. Doskeland SO (1978) Evidence that rabbit muscle protein kinase has two kinetically dis-tinct binding sites for adenosine 3’,5’-cyclic monophosphate. Biochem Biophys Res Commun 83:542–549PubMedGoogle Scholar
  28. Dougherty RW, Niedel JE (1986) Cytosolic calcium regulates phorbol dibutyrate binding affinity in intact phagocytes. J Biol Chem 261:40 97–100Google Scholar
  29. Driedger PE, Blumberg PM (1977) The effect of phorbol diesters on chicken embryo fibroblasts. Cancer Res 37:3257–3265PubMedGoogle Scholar
  30. Farrar WL, Thomas TP, Anderson WB (1985) Altered cytosol/membrane enzyme redistribution on interleukin 3 activation of protein kinase C. Nature 315:235–237PubMedGoogle Scholar
  31. Fleischman LF, Chahwala SB, Cantely L (1986) -transformed cells: altered levels of phosphatidylinositol 4,5-bisphosphate and catabolites. Science 231:407–410PubMedGoogle Scholar
  32. Frantz CN (1985) Effect of platelet-derived growth factor on Ca2+ in 3T3 cells. Exp Cell Res 158:287–300PubMedGoogle Scholar
  33. Froelich JE, Rachmeler M (1972) Effect of adenosine-3’-5’-cyelic monophosphate on cell proliferation. J Cell Biol 55:19–31Google Scholar
  34. Fujiki H, Tanaka Y, Miyake R, Kikkawa U, Nishizuka Y (1984) Activation of calcium activated phospholipid dependent protein kinase (protein kinase C) by a new class of tomour promotors: teleocidin and debromoaplysiatoxin. Biochem Biophys Res Commun 120:339–343PubMedGoogle Scholar
  35. Gardner SD, Milligan G, Rice JE, Wakelam MSO (1989) The effect of cholera toxin on the inhibition of vasopressin stimulated inositol phosphate generation is a cyclic AMP mediated effect at the level of receptor binding. Biochem J 259:679–684PubMedGoogle Scholar
  36. Goodhardt M, Ferry N, Geynet P, Hanoune J (1982) Hepatic ax-adrenergic receptors show agonist specific regulation by guanine nucleotides. J Biol Chem 257:11577–11583PubMedGoogle Scholar
  37. Guillon G, Gallo-Payet N, Balestre MN (1988) Cholera toxin and ACTH modulation of inositol phosphate accumulation induced by vasopressin and angiotensin II in rat glomerulosa cells. Biochem J 253:765–775PubMedGoogle Scholar
  38. Guy GR, Gordon J, Walker I, Michell RH, Brown G (1986) Redistribution of protein kinase C during mitogenesis of human B lymphocytes: Biochem Biophys Res Commun 135:146–153Google Scholar
  39. Hancock JF, Marshall CJ, McKay IA, Gardner S, Houslay MD, Hall A, Wakelam MJO (1988) Mutant but not normal p21ras elevates inositol phospholipid breakdown in two different cell systems. Oncogene 3:187–193PubMedGoogle Scholar
  40. Hesketh TR, Moore JP, Morris JDH, Taylor MY, Rogers J, Smith GA, Metcalfe JC (1985) A common sequence of calcium and pH signals in the mitogenic stimulation of eukaryotic cells. Nature 313:481–484PubMedGoogle Scholar
  41. Hoffman F, Beavo J A, Bechtel PJ, Krebs EG (1975) Comparison of adenosine 3’,5’- monophosphate-dependent protein kinase from rabbit skeletal and bovine heart muscle. J Biol Chem 250:7795–1801Google Scholar
  42. Houslay MD (1985) The insulin receptor and signal generation at the plasma membrane. Mol Asp Cell Reg 5:279–334Google Scholar
  43. Imai A, Gershengorn MC (1986) Phosphatidylinositol 4,5-bisphosphate turnover is transient while phosphatidylinositol turnover is persistent in thyrotropin-releasing hormone-stimulated rat pituitary cells. Proc Natl Acad Sci USA 83:8540–8544PubMedGoogle Scholar
  44. Irvine RF, Moor RM (1986) Microinjection of inositol (1,3,4,5) tetrakisphosphate activates sea urchin eggs by promoting Ca2 + entry. Biochem J 240:917–920PubMedGoogle Scholar
  45. Irvine RF, Moor RM (1987) Inositol (1,3,4,5) tetrakisphosphate-induced activation of sea urchin eggs requires the presence of inositol trisphosphate. Biochem Biophys Res Commun 146:284–290PubMedGoogle Scholar
  46. Irvine RF, Brown KD, Berridge MJ (1984) Specificity of inositol trisphosphate-induced calcium release from permeabilised Swiss-mouse 3T3 cells. Biochem J 222:269–272PubMedGoogle Scholar
  47. Jackowski S, Rettenmier CW, Sherr CJ, Rock CO (1986) A guanine nucleotide-dependent phosphatidylinositol 4,5-diphosphate phospholipase C in cells transformed by the v- fms and v-fes oncogenes. J Biol Chem 261:4978–4985PubMedGoogle Scholar
  48. Jackson TR, Hallam TJ, Downes CP, Hanley MR (1987) Receptor coupled events in bradykinin action: rapid production of inositol phosphates and regulation of cytosolic free Ca2 + in a neural cell line. EMBO J 6:49–54PubMedGoogle Scholar
  49. Jeng AY, Srivastava SJK, Lacal JC, Blumberg PM (1987) Phosphorylation of ras oncogene product by protein kinase C. Biochem Biophys Res Commun 145:782–788PubMedGoogle Scholar
  50. Johnson GS, Friedman RM, Pastan I (1971) Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3/:5/-cyclic monophosphate and its derivatives. Proc Natl Acad Sci USA 68:425–429PubMedGoogle Scholar
  51. Kamata T, Sullivan NF, Wooten MW (1987) Reduced protein kinase C activity in a ras resistant cell line derived from Ki-MSY transformed cells. Oncogene 1:37–46PubMedGoogle Scholar
  52. Kaplan DR, Whitman M, Schaffhausen B, Pallas DC, White M, Cantley L, Roberts RM (1987) Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell 50:1021–1029PubMedGoogle Scholar
  53. Kaplan PL, Anderson M, Ozanne B (1982) Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system. Proc Natl Acad Sci USA 79:485–489PubMedGoogle Scholar
  54. Katsaros D, Tortora G, Tagliaferri P, Clair T, Ally S, Neckers L, Robins RK, Cho-Chung YS (1987) Site selective cyclic AMP analogues provide a new approach in the control of cancer cell growth. FEBS Lett 223:97–103PubMedGoogle Scholar
  55. Kirk CJ, Michell RH, Parry J, Shears SB (1987) Inositol trisphosphate and tetrakisphosphate phosphomonoesterases of rat liver. Biochem Soc Trans 15:28–32PubMedGoogle Scholar
  56. 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 phosphatidylinositol turnover. J Biol Chem 255:2273–2276PubMedGoogle Scholar
  57. Kram R, Mamont P, Tomkins GM (1973) Pleiotypic control by adenosine 3’:5,-cyclic mo-nophosphate: a model for growth control in animals. Proc Natl Acad Sei USA 70:1432–1436Google Scholar
  58. Lacal JC, Fleming TP, Warren BS, Blumberg PM, Aaronson S (1987 a) Involvement of functional protein kinase C in the mitogenic response to the H-ras oncogene product. Mol Cell Biol 7:4146–4149Google Scholar
  59. Lacal JC, de la Pena P, Moscat J, Garcia-Barreno P, Anderson PS, Aaronson SA (1987 b) Rapid stimulation of diacylglycerol production in Xenopus oocytes by micro injection ofH-rasp21. Science 238:533–536PubMedGoogle Scholar
  60. Lacal JC, Moscat J, Aaronson SA (1987 c) Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene. Nature 330:269–272PubMedGoogle Scholar
  61. L’Allemain G, Paris S, Pouyssegur J (1984) Growth factor action and intracellular pH regulation in fibroblasts. J Biol Chem 259:5809–5815PubMedGoogle Scholar
  62. Leal F, Williams LT, Robbins KC, Aaronson SA (1985) Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor. Science 230:327–330PubMedGoogle Scholar
  63. Lloyd AC, Davies SA, Crossley I, Whittaker M, Houslay MD, Hall A, Marshall CJ, Wakelam MJO (1989) Bombesin stimulation of inositol 1,4,5-trisphosphate generation and intracellular calcium release is amplified in a cell line overexpressing the N-ras proto-oncogene. Biochem J 260:813–819PubMedGoogle Scholar
  64. Lo WWY, Hughes J (1987) A novel cholera toxin-sensitive G-protein (Gc) regulating receptor mediated phosphoinositide signalling in human pituitary clonal cells. FEBS Lett 220:327–331Google Scholar
  65. Lopez-Rivas A, Rozengurt E (1983) Serm rapidly mobilises calcium from an intracellular pool in quiescent fibroblastic cells. Biochem Biophys Res Commun 114:240–247PubMedGoogle Scholar
  66. Low MG, Ferguson MAJ, Fukerman AH, Silman I (1986) Covalently attached phosphatidylinositol as a hydrophobic anchor for membrane proteins. Trends Biochem Sei 11:212–215Google Scholar
  67. Majerus PW, Connolly TM, Bansel VS, Inhorn RC, Ross TS, Lips DL (1988) Inositol phosphates: synthesis and degradation. J Biol Chem 263:3051–3054PubMedGoogle Scholar
  68. Markovac J, Goldstein GW (1988) Transforming growth factor beta activates protein kinase C in micro vessels isolated from immature rat brain. Biochem Biophys Res Commun 150:575–582PubMedGoogle Scholar
  69. Matuoka K, Fukami K, Nakanishi P, Kawai S, Takenawa T (1988) Mitogenesis in response to PDGF and bombesin abolished by microinjection of antibody to PIP2. Science 239:640–643PubMedGoogle Scholar
  70. Michell RH (1975) Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta 415:81–147PubMedGoogle Scholar
  71. Milligan G (1988) Techniques used in the identification and analysis of function of pertussis-toxin-sensitive guanine nucleotide binding proteins. Biochem J 255:1–13PubMedGoogle Scholar
  72. Monaco M (1987) Inositol metabolism in WRK-1 cells. Relationship of hormone-sensitive to -insensitive pools of phosphoinositides. J Biol Chem 262:13001–13006PubMedGoogle Scholar
  73. Moolenaar WH, Tsien RY, van der Saag PT, De Laat SW (1983) Na+/H+ exchange and cycloplasmic pH in the action of growth factors in human fibroblasts. Nature 304:645–648PubMedGoogle Scholar
  74. Morris AP, Gallacher DV, Irvine RF, Peterson OH (1987) Synergism of inositol trisphosphate and tetrakisphosphate in activating Ca2+-dependent K+ channels. Naure 330:653–655Google Scholar
  75. Muir JG, Murray AW (1987) Bombesin and phorbol ester stimulate phosphatidylcholine hydrolysis by phospholipase C: evidence for a role of protein kinase C. J Cell Physiol 130:382–391PubMedGoogle Scholar
  76. Murphy GJ, Hruby VJ, Trivedi D, Wakelam MJO, Houslay MD (1987) The rapid desensitization of glucagon-stimulated adenylate cyclase is a cyclic AMP-independent process that can be mimicked by hormones that stimulate inositol phospholipid metabolism. Biochem J 243:39–6Google Scholar
  77. Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308:693–697PubMedGoogle Scholar
  78. Nishizuka Y (1988) The heterogeneity and differential expression of multiple species of the protein kinase C family. Biofactors 1:17–20PubMedGoogle Scholar
  79. Otten J, Johnson GS, Pastan I (1972) Regulation of cell growth by cyclic adenosine 3’,5’- monophosphate. Effect of cell density and agents which alter cell growth on cyclic adenosine -monophosphate levels in fibroblasts. J Biol Chem 247:7082–7087Google Scholar
  80. Owen RD, Ostrowski MC (1987) Rapid and selective alterations in the expression of cellular genes accompany conditional transcription of Ha-v-ras in NIH-3T3 cells. Molec Cell Biol 7:2512–2520PubMedGoogle Scholar
  81. Ozanne B, Fulton RJ, Kaplan PL (1980) Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell line produce transforming factors. J Cell Physiol 105:163–180PubMedGoogle Scholar
  82. Parries G, Hoebel R, Racker E (1987) Opposing effects of a ras oncogene on growth factor stimulated phosphoinositide hydrolysis: desensitization to platelet-derived growth factor and enhanced sensitivity to bradykinin. Proc Natl Acad Sci USA 84:2648–2652PubMedGoogle Scholar
  83. Preiss J, Loomis CR, Bishop WR, Stein R, Niedel JE, Bell RM (1986) Quantitative measurement of sn-t,2-diacylglyeerols in platelets, hepatocytes and ras- and sis- transformed normal rat kidney cells. J Biol Chem 261:8597–8600PubMedGoogle Scholar
  84. Putney JW Jr (1986) A model for receptor regulated calcium entry. Cell Calcium 7:1–12PubMedGoogle Scholar
  85. Rannels SR, Corbin JD (1980) Two different intrachain cAMP binding sites of cAMP- dependent protein kinases. J Biol Chem 255:7085–7088PubMedGoogle Scholar
  86. Ridgeway AAG, DE Vouge MW, Mukerjee BB (1988) Dibutyryl cyclic AMP inhibits expression of transformation related properties in Kirsten murine sarcoma virus transformed Balb/c-3T3 cells despite continued presence of p21 v-Ki-ras. Biochem Cell Biol 66:54–65Google Scholar
  87. Roberts AB, Anzona MA, Wakefield LM, Roche NS, Stern DF, Sporn MB (1985) Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA 82:114–123Google Scholar
  88. Rozengurt E (1985) The mitogenic response of cultured 3T3 cells: integration of early signal and synergistic effects in a unified framework. Mol Asp Cell Reg 5:429–452Google Scholar
  89. Rozengurt E, Legg A, Strang G, Courtnay-Luck N (1981) Cyclic AMP, a mitogenic signal for Swiss 3T3 cells. Proc Natl Acad Sci USA 78:4392–4396PubMedGoogle Scholar
  90. Rudland PS, Weil S, Hunter AR (1975) Changes in RNA metabolism and accumulation of presumptive messenger RNA during transition from the growing to the quiescent state of cultured mouse fibroblasts. J Mol Biol 96:745–766PubMedGoogle Scholar
  91. Saltiel AR, Cuatrecasas P (1986) Insulin stimulates the generation from hepatic plasma membranes of modulators derived from an inositol glycolipid. Proc Natl Acad Sci USA 83:5793–5797PubMedGoogle Scholar
  92. Schliwa M, Nakamura T, Porter KR, Euteneur U (1984) A tumour promotor induces rapid and coordinated reorganisation of actin and vinculin in cultured cells. J Cell Biol 99:1045–1059PubMedGoogle Scholar
  93. Schuldiner S, Rozengurt E (1982) Na+/H+ antiport in Swiss 3T3 cells: mitogenic stimulation leads to cytoplasmic alkalinisation. Proc Natl Acad Sci USA 79:7778–7782PubMedGoogle Scholar
  94. Seuwen K, Lagard A, Pouyssegur J (1988) Deregulation of hamster fibroblast proliferation by mutated ras oncogenes is not mediated by constitutive activation of phosphoinositide specific phospholipase C. EMBO J 7:161–168PubMedGoogle Scholar
  95. Sheppard JR (1972) Difference in the cyclic adenosine 3’,5’-monophosphate levels in normal and transformed cells. Nature New Biol 236:14–16PubMedGoogle Scholar
  96. Sheppard JR, Prescott DM (1972) Cyclic AMP levels in synchronised mammalian cells. Exp Cell Res 75:293–296PubMedGoogle Scholar
  97. Smets LA, Van Rooy H (1987) Mitogenic and antimitogenic effects of cholera toxin-mediated cyclic AMP levels in 3T3 cells. J Cell Physiol 133:395–399PubMedGoogle Scholar
  98. Smith JB, Smith L (1984) Rapid calcium mobilisation by vasopressin and prostaglandin F2a independent of sodium influx in quiescent cells. Biochem Biophys Res Commun 123:803–809PubMedGoogle Scholar
  99. Sporn MB, Roberts AB (1985) Autocrine growth factors and cancer. Nature 313:745–747PubMedGoogle Scholar
  100. Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a non- mitochondrial intracellular store in pancreatic accinar cells by inositol 1,4,5 trisphosphate. Nature 306:67–69PubMedGoogle Scholar
  101. Tagliaferri P, Katsaros D, Clair T, Neckers L, Robins RK, Cho-Chung YS (1988) Reverse transformation of Harvey murine sarcoma virus transformed NIH-3T3 cells by site selective cyclic AMP analogues. J Biol Chem 263:409–416PubMedGoogle Scholar
  102. Trahey M, McCormick F (1987) A cytoplasmic protein stimulates normal N-ras p21Google Scholar
  103. GTPase but does not affect oncogenic mutants. Science 238:542–545Google Scholar
  104. Tucker RF, Volkenant ME, Branum EL, Moses HL (1983) Comparison of intra- and extracellular transforming growth factors from nontransformed and chemically transformed mouse embryo cells. Cancer Res 43:1581–1586PubMedGoogle Scholar
  105. Tucker RF, Shipley GD, Moses HL, Holley RW (1984) Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science 226:705–707PubMedGoogle Scholar
  106. Uno I, Fukami K, Kato H, Takenawa T, Ishikawa T (1988) Essential role for phosphatidylinositol 4,5-bisphosphate in yeast cell proliferation. Nature 333:188–190PubMedGoogle Scholar
  107. Vallar L, Spada A, Giannattasio G (1987) Altered Gs and adenylate cyclase activity in human pituitary adenomas. Nature 330:566–568PubMedGoogle Scholar
  108. Wakelam MJO (1988) Inhibition of the amplified bombesin-stimulated inositol phosphate response in N-ras transformed cells by high density culturing. FEBS Lett 228:182–186PubMedGoogle Scholar
  109. Wakelam MJO (1989) Amplification of fluorocaluminate-stimulated inositol phosphate generation in a cell line overexpressing the p21Nras gene. Biochem J 259:737–741PubMedGoogle Scholar
  110. Wakelam MJO, Murphy GJ, Hruby VJ, Houslay MD (1986 a) Activation of two signal- transduction systems in hepatocytes by glucagon. Nature 323:68–71PubMedGoogle Scholar
  111. Wakelam MJO, Davies SA, Houslay MD, McKay I, Marshall CJ, Hall A (1986 b) Normal p21N_ras couples bombesin and other growth factor receptors to inositol phosphate production. Nature 323:173–176PubMedGoogle Scholar
  112. Wakelam MJO, Houslay MD, Davies SA, Marshall CJ, Hall A (1987) The role of p21N“ras in the coupling of growth factor receptors to inositol phospholipid turnover. Biochem Soc Trans 15:45–47PubMedGoogle Scholar
  113. Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wateson A, Westermark B, Heldin CH, Huang JS, Deuel TF (1983) Platelet-derived growth factor is structurally related to the putative transforming protein p28 sis of simian sarcoma virus. Nature 304:35–39PubMedGoogle Scholar
  114. Werth DK, Pastan I (1984) Vinculin phosphorylation in response to calcium and phorbol esters in intact cells. J Biol Chem 259:5264–5270PubMedGoogle Scholar
  115. Whitfield JF, Durkin JP, Franks DJ, Kleine LP, Raptis L, Rixon RH, Sikorska M, Walker PR (1987) Calcium, cyclic AMP and protein kinase C-partners in mitogenesis. Cancer Metastasis Rev 5:205–250PubMedGoogle Scholar
  116. Whitman M, Kaplan DR, Roberts TM, Cantley L (1987) Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Biochem J 247:165–174PubMedGoogle Scholar
  117. Whitman M, Downes CP, Keeler M, Keller T, Cantley L (1988) Type I phosphatidylinositol kinase makes a novel phospholipid phosphatidylinositol 3- phosphate. Nature 332:644–646PubMedGoogle Scholar
  118. Wolf BA, Comens PG, Ackerman KE, Sherman WR, McDaniel ML (1985) The digitonin- permeabilized pancreatic islet model: effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilisation. Biochem J 227:965–969PubMedGoogle Scholar
  119. Wolfman A, Macara IG (1987) Elevated levels of diacylglycerol and decreased phorbol ester sensitivity in ras-transformed fibroblasts. Nature 325:359–369PubMedGoogle Scholar
  120. Zetterberg A, Larsson O (1985) Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of Swiss albino 3T3 cells. Proc Natl Acad Sci USA 82:5365–5369PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1990

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  • M. J. O. Wakelam

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