Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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).
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).
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).
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).
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).
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).
A. B. Pardee, R. Dubrow, J. L. Hamlin, and R. F. Kletzien. Animal cell cycle. Ann. Rev. Biochem. 47:715, (1978).
K. A. Smith. T-cell growth factor. In Immunological Reviews, 51, G. Moeller ed. Munksgaard, Copenhagen, pp 337–357, (1980).
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).
D. A. Cantrell, and K. A. Smith. The interleukin-2 T-cell system: A new cell growth model. Science 224:1312, (1984).
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).
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).
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).
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).
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).
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).
M. E. Greenberg, and E. B. Ziff. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433, (1984).
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).
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).
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).
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).
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).
J. M. Bishop. Cellular oncogenes and retroviruses. Ann. Rev. Biochem. 52:301, (1983).
K. Kelly, and U. Siebenlist. The regulation and expression of c-myc in normal and malignant cells. Ann. Rev. Immunol. 4:317, (1986).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Plenum Press, New York
About this chapter
Cite this chapter
Kelly, K., Underwood, B. (1987). Cell Growth Associated Regulation of c-myc and c-fos in Normal Human T Cells. In: Gupta, S., Paul, W.E., Fauci, A.S. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation. Advances in Experimental Medicine and Biology, vol 213. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5323-2_24
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5323-2_24
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5325-6
Online ISBN: 978-1-4684-5323-2
eBook Packages: Springer Book Archive