Advertisement

Molecular Mechanisms of Growth and Death Control of Hematopoietic Cells by Cytokines

  • Jeffrey J. Y. Yen
  • Hsin-Fang Yang-Yen
  • Huei-Mei Huang
  • Yueh-Chun Hsieh
  • Shern-Fwu Lee
  • Jyh-Rong Chao
  • Jian-Chuan Lee

Abstract

In responding to the challenge of exogenous antigen(s), there is always a dramatic expansion of certain white blood cell populations in order to achieve tasks of self-defense. It is the cytokines secreted by various immunological cells which are responsible for provoking exponential proliferation and differentiation of these blood cells through binding to their own specific cell surface receptors. Not only the rate of proliferation, but also the length of life span of these blood cells increases. Usually some hundred-fold increase of a single cell population can be achieved within several days. However, once the antigen is eliminated from the body, a rapid clearance of these cell types can be expected within several days which returns the hematopoietic cell population to its normal size. This occurs in response to the decrease in the blood concentration of these essential cytokines. Both rapid expansion of desired cell lineage in emergency and rapid elimination of un-warranted cell population after recovery are characteristics of a successful immune response. Interference in the regulation of above mentioned control always results in immune-pathogenesis. Utilizing the factor-dependent cell line as a model system we are interested in the mechanisms of apoptosis initiation by cytokine deprivation, apoptosis suppression by cytokines, and possibly on the mechanisms underlying leukemogenesis.

Keywords

Tyrosine Phosphorylation Cytokine Receptor Apoptosis Suppression Specific Cell Surface Receptor Death Control 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akira, S., Nishio, Y, Inoue, M., Wang, X. J., Wei, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto, M. and Kishimoto, T. (1994). Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp 130-mediated signaling pathway. Cell 77, 63–71.PubMedCrossRefGoogle Scholar
  2. Cornelis, S., Fache, I., Van-der-Heyden, J., Guisez, Y., Tavernier, J., Devos, R., Fiers, W. and Plaetinck, G. (1995). Characterization of critical residues in the cytoplasmic domain of the human interleukin-5 receptor alpha chain required for growth signal transduction. Eur J Immunol 25, 1857–1864.PubMedCrossRefGoogle Scholar
  3. D’Andrea, R., Rayner, J., Moretti, P., Lopez, A., Goodall, G. J., Gonda, T. J. and Vadas, M. (1994). A mutation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5 that leads to ligand independence and tumorigenicity. Blood 83, 2802–2808.PubMedGoogle Scholar
  4. D’Andrea, R. J., Barry, S. C., Moretti, P. A. B., Jones, K., Ellis, S., Vadas, M. A. and Goodall, G. J. (1996). Extracellular truncations of hβc, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation. Blood 87, 2641–2648.PubMedGoogle Scholar
  5. Darnell, J., Jr., Kerr, I. M. and Stark, G. R. (1994). Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415–1421.PubMedCrossRefGoogle Scholar
  6. Ihle, J. N., Witthuhn, B. A., Quelle, F. W., Yamamoto, K. and Silvennoinen, O. (1995). Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol 13, 369–398.PubMedCrossRefGoogle Scholar
  7. Jenkins, B. J., D’Andrea, R. and Gonda, T. J. (1995). Activating point mutations in the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors suggest the involvement of beta subunit dimerization and cell type-specific molecules in signalling. EMBO J 14, 4276–4287.PubMedGoogle Scholar
  8. Kaplan, M. H., Schindler, U., Smiley, S. T. and Grusby, M. J. (1996). Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells. Immunity 4, 313–319.PubMedCrossRefGoogle Scholar
  9. Kinoshita, T., Yokota, T., Arai, K. and Miyajima, A. (1995). Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors. EMBO J 14, 266–275.PubMedGoogle Scholar
  10. Kishimoto, T., Taga, T. and Akira, S. (1994). Cytokine signal transduction. Cell 76, 253–262.PubMedCrossRefGoogle Scholar
  11. Kitamura, T., Tange, T., Terasawa, T., Chiba, S., Kuwaki, T., Miyagawa, K., Piao, Y. F., Miyazono, K., Urabe, A. and Takaku, F. (1989). Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J Cell Physiol 140, 323–334.PubMedCrossRefGoogle Scholar
  12. Kouro, T., Kikuchi, Y, Kanazawa, H., Hirokawa, K., Harada, N., Shiiba, M., Wakao, H., Takaki, S. and Takatsu, K. (1996). Critical proline residues of the cytoplasmic domain of the IL-5 receptor alpha chain and its function in IL-5-mediated activation of JAK kinase and STAT5. Intl Immunology 8, 237–245.CrossRefGoogle Scholar
  13. Leung, S., Qureshi, S. A., Kerr, I. M., Darnell, J., Jr. and Stark, G. R. (1995). Role of STAT2 in the alpha interferon signaling pathway. Mol Cell Biol 15, 1312–1317.PubMedGoogle Scholar
  14. Mui, A. L., Wakao, H., O’Farrell, A. M., Harada, N. and Miyajima, A. (1995). Interleukin-3, granul ocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J 14, 1166–1175.PubMedGoogle Scholar
  15. Nakajima, K., Yamanaka, Y., Nakae, K., Kojima, H., Ichiba, M., Kiuchi, N., Kitaoka, T., Fukada, T., Hibi, M. and Hirano, T. (1996). A central role for Stat3 in IL-6-induced regulation of growth and differentiation in Ml leukemia cells. EMBO J 15, 3651–3658.PubMedGoogle Scholar
  16. Palacios, R. and Steinmetz, M. (1985). Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell 41, 727–734.PubMedCrossRefGoogle Scholar
  17. Sadowski, H. B., Shuai, K., Darnell, J., Jr. and Gilman, M. Z. (1993). A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science 261, 1739–1744.PubMedCrossRefGoogle Scholar
  18. Sakamaki, K., Miyajima, I., Kitamura, T. and Miyajima, A. (1992). Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. EMBO J 11, 3541–3549.PubMedGoogle Scholar
  19. Sakatsume, M., Igarashi, K., Winestock, K. D., Garotta, G., Larner, A. C. and Finbloom, D. S. (1995). The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors. J Biol Chem 270, 17528–17534.PubMedCrossRefGoogle Scholar
  20. Sato, N., Sakamaki, K., Terada, N., Arai, K. and Miyajima, A. (1993). Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling. EMBO J 12, 4181–4189.PubMedGoogle Scholar
  21. Schindler, C. and Darnell, J., Jr. (1995). Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 64, 621–651.PubMedCrossRefGoogle Scholar
  22. Shuai, K., Ziemiecki, A., Wilks, A. F., Harpur, A. G., Sadowski, H. B., Gilman, M. Z. and Darnell, J. E. (1993). Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature 366, 580–583.PubMedCrossRefGoogle Scholar
  23. Stomski, F. C., Sun, Q., Bagley, C. J., Woodcock, J., Goodall, G., Andrews, R. K., Berndt, M. C. and Lopez, A. F. (1996). Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha-and beta-chain hetrodimerization, which is required for receptor activation but not high-affinity binding. Mol Cell Biol 16, 3035–3046.PubMedGoogle Scholar
  24. Takaki, S., Tominaga, A., Hitoshi, Y, Mita, S., Sonoda, E., Yamaguchi, N. and Takatsu, K. (1990). Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J 9, 4367–4374.PubMedGoogle Scholar
  25. Velazquez, L., Fellous, M., Stark, G. R. and Pellegrini, S. (1992). A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell 70, 313–322.PubMedCrossRefGoogle Scholar
  26. Watling, D., Guschin, D., Muller, M., Silvennoinen, O., Witthuhn, B. A., Quelle, F. W., Rogers, N. C., Schindler, C., Stark, G. R. and Ihle, J. N., et al. (1993). Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-gamma signal transduction pathway. Nature 366, 166–170.PubMedCrossRefGoogle Scholar
  27. Yen, J. J., Hsieh, Y. C., Yen, C. L., Chang, C. C., Lin, S. and Yang-Yen, H. F. (1995). Restoring the apoptosis suppression response to IL-5 confers on erythroleukemic cells a phenotype of IL-5-dependent growth. J Immunol 154, 2144–2152.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Jeffrey J. Y. Yen
    • 1
  • Hsin-Fang Yang-Yen
    • 2
  • Huei-Mei Huang
    • 1
  • Yueh-Chun Hsieh
    • 1
  • Shern-Fwu Lee
    • 1
  • Jyh-Rong Chao
    • 2
  • Jian-Chuan Lee
    • 2
  1. 1.Institute of Biomedical SciencesAcademia SinicaTaipeiTaiwan
  2. 2.Institute of Molecular BiologyAcademia SinicaTaipeiTaiwan

Personalised recommendations