Cell Growth Associated Regulation of c-myc and c-fos in Normal Human T Cells

  • Kathleen Kelly
  • Brenda Underwood
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 213)


The mechanism whereby a quiescent lymphocyte is activated to proliferate and express differentiated functions is a fundamental question for understanding immune regulation and growth control. The binding of ligands such as antigen, mitogenic lectins, and some cell surface-specific antibodies to their membrane receptors on lymphocytes generates a transmembrane signal resulting in a variety of metabolic changes culminating after 24 hours in DNA synthesis (1,2). One initial consequence of transmembrane signalling is the expression of mRNA species novel to activated cells. For example, the cellular proto-oncogene c-myc (3), the T cell growth factor, IL-2 (4), and the IL-2 receptor (5,6) increase expression within approximately 1, 12, and 6 hours, respectively, following mitogenic stimulation of T cells. In additional mRNA species, the proto-oncogene c-fos, between 30 and 90 minutes after PHA addition to human T cells. Such increases occur in the presence of protein syrithesis inhibitors (3,6), indicating that mRNA induction is a direct result of the signals that follow receptor binding and as such probably represent primary transcriptional events.


Competence Gene Centrifugal Elutriation Burkitt Lymphoma Cell Representative Cell Volume Mitogenic Lectin 
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. 1.
    R. Erard, M. Nabholz, A. Dupuy-D’Angeac, and H. R. MacDonald. Differential requirements for the induction of interleukin 2 responsiveness in L3T4+ and Lyt-2+ T cell subsets. J. Exp. Med. 162:1738, (1985).CrossRefGoogle Scholar
  2. 2.
    S. C. Meuer, R. E. Hussey, D. A. Cantrell, J. D. Hogdon, S. F. Schlossman, K. A. Smith, and E. L. Reinherz. Triggering of the T3-Ti antigen receptor complex results in clonal T cell proliferation through an interleukin-2-dependent autocrine pathway. Proc. Natl. Acad. Sci. USA 81:1509, (1984).ADSCrossRefGoogle Scholar
  3. 3.
    K. Kelly, B. Cochran, C. Stiles, and P. Leder. Cell specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603, (1983).CrossRefGoogle Scholar
  4. 4.
    S. Efrat, S. Pilo, and R. Kaempfer. Kinetics of induction and molecular size of mRNAs encoding human interleukin-2 and interferon. Nature 297:236, (1982).ADSCrossRefGoogle Scholar
  5. 5.
    W. J. Leonard, J. M. Depper, G. R. Crabtree, S. Rudikoff, J. Pumphrey, R. Robb, M. Kronke, P. B. Svetlik, N. J. Peffer, T. A. Waldman, and W. C. Greene. Molecular cloning and expression of cDNA for the human interleukin-2 receptor. Nature 311:626, (1984).ADSCrossRefGoogle Scholar
  6. 6.
    M. Kronke, W. J. Leonard, J. M. Depper, and W. C. Greene. Sequential expression of genes involved in human T lymphocyte growth and differentiation. J. Exp. Med. 161:1593, (1985).CrossRefGoogle Scholar
  7. 7.
    A. B. Pardee, R. Dubrow, J. L. Hamlin, and R. F. Kletzien. Animal cell cycle. Ann. Rev. Biochem. 47:715, (1978).CrossRefGoogle Scholar
  8. 8.
    K. A. Smith. T-cell growth factor. In Immunological Reviews, 51, G. Moeller ed. Munksgaard, Copenhagen, pp 337–357, (1980).Google Scholar
  9. 9.
    J. H. Kehrl, A. Muraguchi, J. L. Butler, J. M. Falkoff, and A. S. Fauci. Human B cell activation, proliferation and differentiation. In Immunological Reviews 78, G. Moeller ed., Munksgaard, Copenhagen, pp 75–96, (1984).Google Scholar
  10. 10.
    D. A. Cantrell, and K. A. Smith. The interleukin-2 T-cell system: A new cell growth model. Science 224:1312, (1984).ADSCrossRefGoogle Scholar
  11. 11.
    A. Muraguchi, J. L. Butler, J. H. Kehrl, and A. S. Fauci. Differential sensitivity of human B cell subsets to activation signals delivered by a monoclonal B cell factor. J. Exp. Med. 154:530, (1983).CrossRefGoogle Scholar
  12. 12.
    J. M. Chirgwin, A. E. Przybyla, R. J. MacDonald, and W. J. Rutter. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 16:5294, (1979).CrossRefGoogle Scholar
  13. 13.
    R. Taub, C. Moulding, J. Battey, W. Murphy, T. Vasicek, G. M. Lenoir, and P. Leder. Activation and somatic mutation of the translocated c-myc gene in Burkitt lymphoma cells. Cell 36:339, (1984).CrossRefGoogle Scholar
  14. 14.
    J. Battey, C. Moulding, R. Taub, W. Murphy, T. Stewart, H. Potter, G. Lenoir, and P. Leder. The human c-myc oncogene: Structural consequences of translocation into the IgH in Burkitt lymphoma. Cell 34:779, (1983).CrossRefGoogle Scholar
  15. 15.
    T. Curran, G. Peters, C. Van Beveren, N. M. Teich, and I. Verma FBJ murine osteosarcoma virus: Identification and molecular cloning of biologically active proviral DNA. J. Virology 44:674, (1982).Google Scholar
  16. 16.
    S. V. Suggs, R. B. Wallace, T. Hirose, E. H. Kawashima, and K. Itakura. Use of synthetic oligonucleotides as hybridization probes: Isolation of cloned cDNA sequences for human β2-microglobulin. Proc. Natl. Acad. Sci. USA 78:6613, (1981).ADSCrossRefGoogle Scholar
  17. 17.
    M. E. Greenberg, and E. B. Ziff. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433, (1984).ADSCrossRefGoogle Scholar
  18. 18.
    R. Muller, R. Bravo, J. Burckhardt, and T. Curran. Immediate dramatic induction of c-fos by growth factors precedes activation of c-myc. Nature 312:711, (1984).ADSCrossRefGoogle Scholar
  19. 19.
    B. H. Cochran, A. C. Reffel, and C. D. Stiles. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell 33:413, (1983).CrossRefGoogle Scholar
  20. 20.
    R. Makino, K. Hayashi, and T. Sugimura. c-myc transcript is induced inn rat liver at a very early stage of regeneration or by cycloheximide treatment. Nature 310:697, (1984).ADSCrossRefGoogle Scholar
  21. 21.
    C. B. Thompson, P. B. Challoner, P. E. Neiman, and M. Groudine. Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. Nature 314:363, (1985).ADSCrossRefGoogle Scholar
  22. 22.
    S. R. Hann, C. B. Thompson, and R. N. Eisenman. c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. Nature 314:366, (1985).ADSCrossRefGoogle Scholar
  23. 23.
    J. M. Bishop. Cellular oncogenes and retroviruses. Ann. Rev. Biochem. 52:301, (1983).CrossRefGoogle Scholar
  24. 24.
    K. Kelly, and U. Siebenlist. The regulation and expression of c-myc in normal and malignant cells. Ann. Rev. Immunol. 4:317, (1986).CrossRefGoogle Scholar
  25. 25.
    U. R. Rapp, J. L. Cleveland, K. Brightman, A. Scott, and J. N. Ihle. Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes. Nature 3127:434, (1985).ADSCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Kathleen Kelly
    • 1
  • Brenda Underwood
    • 1
  1. 1.Immunology Branch, NCIBethesdaUSA

Personalised recommendations