The Network of Intracellular Signal Processing as a Main Site of Cellular Responses in Toxicity

  • Friedrich Marks
Conference paper
Part of the NATO ASI Series book series (volume 93)


The ability to communicate is one of the characteristic properties of cells and may actually be considered as the fundamental condition of life. Communication takes place through the exchange of signals. Biological signals are symbols, i.e. they have a distinct meaning. To respond adequately the receiver has to both recognize and decipher a signal. For this purpose prior information is required, which may either have been acquired or is genetically fixed.


Phorbol Ester Okadaic Acid Tumor Promoter Mitogenic Signal Intrinsic GTPase 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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abraham RT, Karnitz LM, Secrist JP & Leibson PJ (1992) Signal transduction through the T-cell antigen receptor. Trends in Biochem Sci 17: 434–438CrossRefGoogle Scholar
  2. Barritt GJ (1992) Communication within animal cells. Oxford Univ Press, Oxford etc.Google Scholar
  3. Baser A (1993) The potential of protein kinase C as a target for anticancer treatment. Pharmac Ther 59: 257–280CrossRefGoogle Scholar
  4. Black ID (1991) Information in the brain. MIT Press Cambridge (Mass.)Google Scholar
  5. Boege F, Neumann E & Helmreich EJM (1991) Structural heterogeneity of membrane receptors and GTP-binding proteins and its functional consequences for signal transduction. Europ J Biochem 199: 1–15PubMedCrossRefGoogle Scholar
  6. Bourne HR, Sanders DA & McCormick F (1991) The GTPase super-family. Nature 348:125–132 and 349: 117–127Google Scholar
  7. Burns SM & Ashwell JD (1993) ZAPping the T-cell receptor. Current Biology 3: 97–99PubMedCrossRefGoogle Scholar
  8. Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R & Soltoff S (1991) Oncogenes and signal transduction. Cell 64: 281–302PubMedCrossRefGoogle Scholar
  9. Cobrinik A, Dowdy SF, Hinds PH, Mittnacht S & Weinberg RA (1992) The retinoblastoma protein and the regulation of cell cylcing. Trends in Biochem Sci 17: 312–315CrossRefGoogle Scholar
  10. Dekker LV, Parker PJ (1994) Protein kinase C - a question of specificity. TIBS 19: 73–77PubMedGoogle Scholar
  11. Diekmann D, Brill S, Garrett MD, Totty N, Hsuan J, Monfries C, Hall C, Lim L & Hall A (1991) Brc encodes a GTPase- activating protein for p21rac. Nature 351: 400–402PubMedCrossRefGoogle Scholar
  12. Dohlman HG, Caron MG & Lefkowitz R (1987) A family of receptors coupled to guanine nucleotide regulatory proteins. Biochemistry 26: 2657–2664PubMedCrossRefGoogle Scholar
  13. Dvorak HF (1986) Tumors: wounds that do not heal. N Engl J Med 315: 1650–1659PubMedCrossRefGoogle Scholar
  14. Fearon ER & Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767PubMedCrossRefGoogle Scholar
  15. Findlay J & Eliopoulos E (1990) Three-dimensional modelling of G-proteins linked receptors. Trends in Pharmacol Sci 11: 492–499CrossRefGoogle Scholar
  16. Fujiki H (1992) Is the inhibitor of protein phosphatase 1 and 2A activities a general mechanism of tumor promotion in human cancer development ? Molec Carcinogenesis 5: 91–94CrossRefGoogle Scholar
  17. Grasso P, Sharratt M & Cohen AJ (1991) Role of persistent, non- genotoxic tissue damage in rodent cancer and relevance to humans. Annu Rev Pharmacol Toxicol 31: 253–287PubMedCrossRefGoogle Scholar
  18. Green S (1992) Nuclear receptors and chemical carcinogenesis. Trends in Pharmacol Sci 13: 251–255CrossRefGoogle Scholar
  19. Gschwendt M, Leibersperger H & Marks F (1989) Differentiative action of U252a on protein kinase C and a calcium- unresponsive, phorbol ester/phospholipd-activated protein kinase. Biochem Biophys Res Commun 164: 974–982PubMedCrossRefGoogle Scholar
  20. Gschwendt M, Kittstein W & Marks F (1991) Protein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role ? TIBS 16: 167–169PubMedGoogle Scholar
  21. Gschwendt M, Kittstein W, Lindner D & Marks F (1992) Differential inhibition by staurosporine of phorbol ester, bryostatin and okadaic acid effects on mouse skin. Cancer Lett 66: 139–146PubMedCrossRefGoogle Scholar
  22. Gulbins E, Coggershall KM, Wittinghofer A, Burn P, Katzar S & Altman A (1994) Dual regulation of the Ras-exchange protein vav by diglycerides and tyrosines. J Cell Biochem Suppl 18B: 257Google Scholar
  23. Gutman A & Wasylyk B (1991) Nuclear targets for transcription regulation by oncogenes. Trends in Genetics 7: 49–54PubMedGoogle Scholar
  24. Haddow A (1972) Molecular repair, wound healing and carcinogenesis: tumour production a possible overhealing ? Adv Cancer Res 16: 181–234PubMedCrossRefGoogle Scholar
  25. Hargave PA & McDowell JH (1992) Rhodopsin and phototransduction: a model system for G-protein linked receptors. FASEB J 6: 2322–2331Google Scholar
  26. Hepler JR & Gilman AG (1992) G-Proteins. Trends in Biochem Sci 17: 383–327CrossRefGoogle Scholar
  27. Hunter T (1991) Protein kinase classification. Methods in Enzymol 200: 3–37CrossRefGoogle Scholar
  28. Hunter T & Karin M (1992) The regulation of transcription by phosphorylation. Cell 70: 375–387PubMedCrossRefGoogle Scholar
  29. Izquierdo M & Cantrell DA (1992) T-cell activation. Trends in Cell Biol 2: 268–271CrossRefGoogle Scholar
  30. Jackson SP (1992) Regulating transcription factor activation by phosphorylation. Trends in Cell Biol 2: 104–108CrossRefGoogle Scholar
  31. Karin M & Smeal T (1992) Control of transcription factors by signal transduction pathways: the beginning of the end. Trends in Biochem Sci 17: 418–422CrossRefGoogle Scholar
  32. Lancer D & Ben-Aric N (1993) Olfactory receptors. Current Biology 3: 668–674CrossRefGoogle Scholar
  33. Lefkowitz RJ (1993) G-protein-coupled receptor kinases. Cell 74: 409–412PubMedCrossRefGoogle Scholar
  34. Leibersperger H, Gschwendt M, Gernold M, Marks F (1991) Immunological demonstration of a calcium-unresponsive protein kinase C of the 5-type in different species and murine tissues. J Biol Chem 266: 14778–14784PubMedGoogle Scholar
  35. Levine AJ, Momand J & Finlay CA (1991) The p53 tumor suppressor gene. Nature 351: 453–456PubMedCrossRefGoogle Scholar
  36. Lindner ME & Gilman AG (1992) G-proteins. Sientific American 267: 36–43Google Scholar
  37. McMahon SB & Monroe JG (1992) Role of primary responses genes in generating cellular responses to growth factors. FASEB J 6: 2707–2715PubMedGoogle Scholar
  38. Marks F (1989) Skin cancer (excluding melanomas). In: Handbook of Exp Pharmacol, vol 87/11, Pharmacology of the Skin II, Greaves MW, Schuster S, eds, Springer-Verlag, Berlin etc. p 165–194Google Scholar
  39. Marks F (1989) Chemical carcinogenesis - the multistage approach. Interdisc Sci Rev 14: 233–240Google Scholar
  40. Marks F & Fürstenberger G (1994) Tumor promotion in the skin. In: Chemical Induction of Cancer, Vol IV, Arcos JC, ed, Academic PressGoogle Scholar
  41. Marks F & Fürstenberger G (1990) The conversion stage of skin carcinogenesis. Carcinogenesis 11: 2085–2092PubMedCrossRefGoogle Scholar
  42. Marks F, Fürstenberger G & Gschwendt M (1992) Skin tumour promotion and the wound response: two sides of a coin. In: The Environmental Threat of the Skin ( Marks F, Fürstenberger G & Gschwendt M, eds), p 297–307, Dunitz London.Google Scholar
  43. Marshall MS (1993) The effector interactions of p21ras. Trends in Biochem Sci 18: 250–254CrossRefGoogle Scholar
  44. Marshall CJ (1991) Tumor suppressor genes. Cell 64: 313–326PubMedCrossRefGoogle Scholar
  45. Murray AW & Kirschner MW (1991) What controls the cell cycle. Scientific American 264: 34–41CrossRefGoogle Scholar
  46. Murray AW (1993) Turning on mitosis. Current Biology 3: 291–293PubMedCrossRefGoogle Scholar
  47. Musacchio A, Gibson T, Rice P, Thompson J & Saraste M (1993) The PH domain: a common piece in the structural patchwork of signalling proteins. Trends in Biochem Sci 18: 343–348CrossRefGoogle Scholar
  48. Mustelin T & Burn P (1993) Regulation of src family tyrosine kinases in lymphocytes. Trends in Biochem Sci 18: 215–220CrossRefGoogle Scholar
  49. Nakanishi H, Brewerk A & Exton JH (1993) Activation of the fisozyme of protein kinase C by phosphatidyl inositol 3,4,5- trisphosphate. J Biol Chem 268: 13–16PubMedGoogle Scholar
  50. Nigg EA (1993) Cellular substrates of p34cdc2 and its companion cylcin-dependent kinases. Trends in Cell Biol 3: 296–301CrossRefGoogle Scholar
  51. Nurse P (1990) Universal control mechanism regulating onset of M-phase. Nature 344: 503–507PubMedCrossRefGoogle Scholar
  52. Orth J (1911) Präcarcinomatöse Krankheiten und künstliche Krebse. Z Krebsforsch 10: 42CrossRefGoogle Scholar
  53. Parkinson JS (1993) Signal transduction schemes of bacteria. Cell 73: 856–871CrossRefGoogle Scholar
  54. Pawson T & Schlessinger J (1993) SH2 and SH3 domains. Current Biology 3: 434–442PubMedCrossRefGoogle Scholar
  55. Pearson RB & Kemp BE (1991) Protein kinase phosphorylation site sequences and consensus specificity motifs. Methods in Enzymol 200: 62–81CrossRefGoogle Scholar
  56. Perera FP (1991) Perspectives on the risk assessment for nongenotoxic carcinogens and tumor promoters. Environ Health Perspect 94: 231–235PubMedCrossRefGoogle Scholar
  57. Poellinger L, Göttlicher M & Gustafsson JA (1992) The dioxin and peroxisome proliferator-activated receptors: nuclear receptors in search of endogenous ligands. Trends in Pharmacol Sci 13: 241–245CrossRefGoogle Scholar
  58. Rahmsdof HJ & Herrlich P (1990) Regulation of gene expression by tumor promoters. Pharmac Ther 48: 157–188CrossRefGoogle Scholar
  59. Reichel RR & Jacob ST (1993) Control of gene expression by lipophilic hormones. FASEB J 7: 427–436PubMedGoogle Scholar
  60. Ross EM (1992) Twists and turns on G-protein signaling pathways. Current Bioloy 2: 517–519CrossRefGoogle Scholar
  61. Schlessinger J & Ullrich A (1992) Growth factor signalling by receptor tyrosine kinases. Neuron 9: 383–391PubMedCrossRefGoogle Scholar
  62. Stabel S & Parker PJ (1991) Protein kinase C. Pharmac Ther 51: 71–95CrossRefGoogle Scholar
  63. Takai Y, Kaibuchi K, Kikuchi A & Kawata M (1992) Small GTP- binding proteins. Int Rev Cytol 133: 187–227PubMedCrossRefGoogle Scholar
  64. Tan YH (1993) Yin and Yang of phosphorylation in cytokine signaling. Science 262: 376–377PubMedCrossRefGoogle Scholar
  65. Wilson CJ & Applebury ML (1993) Arresting G-protein coupled receptor activity. Current Biology 3: 683–686PubMedCrossRefGoogle Scholar
  66. Wynford-Thomas D (1991) Oncogenes and anti-oncogenes; the molecular basis of tumour behaviour. J Pathol 165: 187–201PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Friedrich Marks
    • 1
  1. 1.Research Program Tumor Cell RegulationGerman Cancer Research CenterHeidelbergGermany

Personalised recommendations