Regulation of c-fos Expression by Voltage-Dependent Calcium Channels

  • James I. Morgan
  • Tom Curran
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


The determination of cell function is mediated to a significant degree by dynamic alterations in the intracellular concentration of free calcium. To date, the study of the role of calcium as a second messenger has been largely confined to the analysis of rapid events triggered by this cation that mostly involve posttranslational modification. However, recently it has been recognized that agents that provoke an influx of calcium ions into PC12 cells elicit a rapid, transient, transcriptional activation of thefosprotooncogene (Morgan and Curran, 1986; Greenberget al., 1986). This has led to the proposition (Fig. 1) that c-fosis but one member of a family of cellular immediate-early genes that are induced following stimulation and that act to modulate the long-term responses of a cell. As c-fosencodes a nuclear protein (Curranet al., 1984), it is assumed that these inducible genes are themselves involved in the activation and/or repression of further sets of genes that are responsible for such phe nomena as plasticity, adaptation, long-term potentiation, etc. This study will elaborate the evidence for the involvement of calcium in the regulation of both c-fosexpression and the posttranslational modification of its protein product (Fos).


PC12 Cell Nerve Growth Factor Calcium Channel Antagonist Extracellular Calcium Calmodulin Inhibitor 
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  1. Curran, T., 1988, The fos oncogene, in: The Oncogene Handbook (E. P. Reddy, A. M. Skalka, and T. Curran, eds.), pp. 307–325, Elsevier, Amsterdam.Google Scholar
  2. Curran, T., and Morgan, J. I., 1985, Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines, Science 229:1265–1268.PubMedCrossRefGoogle Scholar
  3. Curran, T., and Morgan, J. I., 1986, Barium modulates c-fos expression and post-translational modi fication, Proc. Natl. Acad. Sci. USA 83:8521–8524.PubMedCrossRefGoogle Scholar
  4. Curran, T., and Teich, N.M., 1982, Candidate product of the FBJ murine osteosarcoma virus oncogene: Characterization of 55,000 dalton phosphoprotein, J. Virol. 42:114-122.PubMedGoogle Scholar
  5. Curran, T., and Verma, I. M., 1984, The FBR murine osteosarcoma virus. I. Molecular analysis and characterization of a 75,000 Da gag-fos fusion product, Virology 135:218–228.Google Scholar
  6. Curran, T., Peters, G., Van Beveren, C., Teich, N. M., and Verma, I. M. 1982, FBJ murine osteosarcoma virus: Identification and molecular cloning of biologically active proviral DNA, J. Virol. 44:674–682.PubMedGoogle Scholar
  7. Curran, T., Miller, A. D., Zokas, L., and Verma, I. M., 1984, Viral and cellular fos proteins: A comparative analysis, Cell 36:259–268.PubMedCrossRefGoogle Scholar
  8. Greenberg, M. E., Ziff, E. B., and Greene, L. A., 1986, Stimulation of neuronal acetylcholine receptors induces rapid gene transcription, Science 234:80–83.PubMedCrossRefGoogle Scholar
  9. Greene, L. A., and Tischler, A. S., 1976, Establishment of a noradrenergic clonal cell line of rat adrenal pheochromocytoma cells which respond to nerve growth factor, Proc. Natl. Acad. Sci. USA 73: 2424–2428.PubMedCrossRefGoogle Scholar
  10. Greene, L. A., and Tischler, A. S., 1982, PC 12 pheochromocytoma cultures in neurobiological research, Advanc. Cell. Neurobiol. 3:373–414.Google Scholar
  11. Morgan, J. I., and Curran, T., 1986, Role of ion flux in the control of c-fos expression, Nature 322: 552–555.PubMedCrossRefGoogle Scholar
  12. Muller, R., Bravo, R., Burckhardt, J., and Curran, T., 1984, Induction of c-fos gene by protein growth factors precedes activation of c-myc, Nature 312:716–720.PubMedCrossRefGoogle Scholar
  13. Sambucetti, L. C., and Curran, T., 1986, The Fos protein complex is associated with DNA in isolated nuclei and binds to DNA cellulose, Science 234:1417–1419.PubMedCrossRefGoogle Scholar
  14. Shin, C., Pedersen, H. B., and McNamara, J. O., 1985, γ-aminobutyric acid and benzodiazepine receptors in the kindling model of epilepsy: A quantitative radiohistochemical study, J. Neurosci. 5:2696–2701.PubMedGoogle Scholar
  15. Traynor, A., and Schubert, D., 1984, Phospholipases elevate cyclicAMP levels and promote neunte extension in a clonal nerve cell line, Dev. Brain Res. 14:197–204.Google Scholar
  16. Valdes, F., Dashieff, R. M., Birmingham, F., Crutcher, K. A., and McNamara, J. O., 1982. Ben zodiazepine receptor increases after repeated seizures: Evidence for localization to dentate granule cells, Proc. Natl. Acad. Sci. USA 79:193–197.PubMedCrossRefGoogle Scholar
  17. Van Beveren, C., Enami, S., Curran, T., and Verma, I. M., 1984, The FBR murine osteosarcoma virus. II. Nucleotide sequence of the provirus reveals that the genome contains sequences derived from two cellular genes, Virology 135:229–243.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • James I. Morgan
    • 1
  • Tom Curran
    • 2
  1. 1.Department of NeurosciencesRoche Institute of Molecular Biology, Roche Research CenterNutleyUSA
  2. 2.Department of Molecular OncologyRoche Institute of Molecular Biology, Roche Research CenterNutleyUSA

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