Signal Transduction from the Haematopoietic Growth Factor Receptors

  • I. P. Touw
Chapter
Part of the Developments in Hematology and Immunology book series (DIHI, volume 32)

Abstract

Haematopoietic growth factors (HGFs) act on the haematopoietic cells via binding to specific cell surface receptors. Many HGF receptors (HGF-R) have certain common structural features and have therefore been grouped in the superfamily of haematopoietin or cytokine receptors also referred to as the class I receptor super-family [1,2]. Activation of these receptors by their respective HGFs is mediated through the formation of dimeric or oligomeric complexes of receptor structures. Some haematopoietin receptors are composed of heteromeric complexes, comprising two or three different receptor chains. For instance this is the case for receptors of interleukin IL-2, IL-3, IL-5, and granulocytemacrophage colony stimulating factor (GM-CSF) [3]. Other receptor structures, e.g., those of granulocyte-CSF (G-CSF) and erythropoietin (EPO), form homodimeric complexes upon growth factor binding [2,4]. This concise overview will start with an introduction to the basic principles of HGF-R signaling. Subsequently, a selection of the recent results obtained in this dynamic area of research, and their implications for our insights in the regulation of normal haematopoietic cell development as well as for understanding disease mechanisms will be briefly discussed.

Keywords

Tyrosine Leukemia Serine Interferon Resi 

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References

  1. 1.
    Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA 1990;87:6934–38.PubMedCrossRefGoogle Scholar
  2. 2.
    Cosman D. The haematopoietin receptor superfamily. Cytokine 1993;5:95–106.PubMedCrossRefGoogle Scholar
  3. 3.
    Miyajima A, Mui ALF, Ogorochi T, Sakamaki K. Receptors for granulocyte macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Blood 1993;82: 1960–74.PubMedGoogle Scholar
  4. 4.
    Fukunaga R, Ishizaka-Ikeda E, Pan C-X, Seto Y Nagata S.Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 1991;10:2855–65.PubMedGoogle Scholar
  5. 5.
    Dong F, Van Buitenen C, Pouwels K, Hoefsloot LH, Löwenberg B, Touw IP. Distinct cytoplasmic regions of the granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation. Mol Cell Biol 1993;13:7774–81PubMedGoogle Scholar
  6. 6.
    Yamanaka Y Nakajima K, Fukada T, Hibi M, Hirano T. Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for STAT3 activation. EMBO J 1996;15:1557–65.PubMedGoogle Scholar
  7. 7.
    Porteu F, Rouyez M-C, Cocault L, et al. Functional regions of the mouse thrombo-poietin receptor cytoplasmic domain: Evidence for a critical region which is involved in differentiation and can be complemented by erythropoietin. Mol Cell Biol 1996; 16:2473–82.PubMedGoogle Scholar
  8. 8.
    Ihle JN, Kerr IM. JAKs and STATS in signaling by the cytokine receptor superfamily.Google Scholar
  9. Trends Genet 1995;11:69–74.Google Scholar
  10. 9.
    Quelle FW, Sato N, Witthuhn BA, et al. JAK2 associates with the βc chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. Mol Cell Biol 1994;14:4335–4.PubMedGoogle Scholar
  11. 10.
    Miura O, Cleveland JL, Ihle JN. Inactivation of erythropoietin receptor function by point mutations in a region having homology with other cytokine receptors. Mol Cell Biol 1993;13:1788–95.PubMedGoogle Scholar
  12. 11.
    Zhuang H, Patel SV, He T, Sonsteby S, Niu Z, Wojchowski DM. Inhibition of ery-thropoietin-induced mitogenesis by a kinase-deficient form of JAK2. J Biol Chem 1994;269:21411–14.PubMedGoogle Scholar
  13. 12.
    Meraz MA, White JM, Sheehan KCF, et al. Targeted disruption of the STAT1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 1996;84:431–42.PubMedCrossRefGoogle Scholar
  14. 13.
    Durbin JE, Hackenmiller R, Simon MC, Levy DE. Targeted disruption of the mouse STAT1 gene results in compromised innate immunity to viral disease. Cell 1996;85: 443–50.CrossRefGoogle Scholar
  15. 14.
    Nakajima K, Yamanaka Y, Nakae K, et al. A central role for STAT3 in IL-6-induced regulation of growth and differentiation in Ml leukemia cells. EMBO J 1996;15: 3651–58.PubMedGoogle Scholar
  16. 15.
    Thierfelder WE, van Deursen JM, Yamamoto K, et al. Requirement for STAT4 in interleukin-12 mediated responses of natural killer cells. Nature 1996;382:171–74.PubMedCrossRefGoogle Scholar
  17. 16.
    Kaplan MH, Sun Y-L, Hoey T, Grusby MJ. Impaired IL-I2 responses and enhanced development of Th cells in STAT-4-deficient mice. Nature 1996;382:174–77.PubMedCrossRefGoogle Scholar
  18. 17.
    Mui ALF, Wakao H, O’Farrell AM, Harada N, Miyajima A. Interleukin-3, granulocyte macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J 1995;14:1166–75.PubMedGoogle Scholar
  19. 18.
    Takeda K, Tanaka T, Shi W, et al. Essential role of STAT6 in IL-4 signaling. Nature 1996;380:627–30.PubMedCrossRefGoogle Scholar
  20. 19.
    Shimoda K, van Deursen J, Sangster MY, et al. Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted STAT6 gene. Nature 1996;380: 630–33.PubMedCrossRefGoogle Scholar
  21. 20.
    Barge RMY, de Koning JP, Pouwels K, Dong F, Löwenberg B, Touw IP. Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G-CSF-mediated activation of signaling complexes of the p21Ras route. Blood 1996;87:2148–53.PubMedGoogle Scholar
  22. 21.
    Wen Z, Zhong Z, Darnell JE. Maximal activation of transcription by STAT1 and STAT3 requires both tyrosine and serine phosphorylation. Cell 1995;82:241–50.PubMedCrossRefGoogle Scholar
  23. 22.
    David M, Petricoin III E, Benjamin C, Pine R, Weber MJ, Larner A-C. Requirement for MAP kinase (ERK2) activity in interferon a- and interferon β-stimulated gene expression through STAT proteins. Science 1995;269: 1721–23.PubMedCrossRefGoogle Scholar
  24. 23.
    Longmore GD, Lodish HF. An activating mutation in the murine erythropoietin receptor induces erythroleukemia in mice: A cytokine receptor superfamily oncogene. Cell 1991,67: 1089–102.PubMedCrossRefGoogle Scholar
  25. 24.
    Noguchi M, Yi H, Rosenblatt HM, et al. Interleukin-2 receptor y chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 1993;73:147–57.PubMedCrossRefGoogle Scholar
  26. 25.
    Nosaka T, van Deursen J MA, Tripp, et al. Defective lymphoid development in mice lacking JAK3. Science 1995;270:800–2.PubMedCrossRefGoogle Scholar
  27. 26.
    Russell SM, Tayebi N, Nakajima H, et al. Mutation of JAK3 in a patient with SCID: Essential role of JAK3 in lymphoid development. Science 1995;270:797–800.PubMedCrossRefGoogle Scholar
  28. 27.
    De la Chapelle A, Träskelin AL, Juvonen E. Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. Proc Natl Acad Sci USA 1993;90: 4495–99.PubMedCrossRefGoogle Scholar
  29. 28.
    Sokol L, Luhovy M, Guan y, Prchal JF, Semenza GL, Prchal JT. Primary familial polycythemia: A frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin. Blood 1995;86:15–22.PubMedGoogle Scholar
  30. 29.
    Klingmüller U, Lorenz U, Cantley LC, Neel BG, Lodish HF. Specific recruitment of SH-PTP 1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell 1995;80:729–38.PubMedCrossRefGoogle Scholar
  31. 30.
    Dong F, Hoefsloot LH, Schelen AM, et al. Identification of a nonsense mutation in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia. Proc Natl Acad Sci USA 1994;91:4480–84.PubMedCrossRefGoogle Scholar
  32. 31.
    Dong F, Brynes RK, Tidow N, Weite K, Löwenberg B, Touw IP. Mutations truncating the C-terminal maturation region of the G-CSF receptor in acute myeloid leukemia preceded by severe congenital neutropenia. N Engl J Med 1995;333: 487–93.PubMedCrossRefGoogle Scholar
  33. 32.
    Dong F, van Paassen M, van Buitenen C, Hoefsloot LH, Löwenberg B, Touw IP. A point mutation in the granulocyte colony-stimulating factor receptor (G-CSF-R) gene in a case of acute myeloid leukemia results in the overexpression of a novel G-CSF-R isoform. Blood 1995;85:902–11.PubMedGoogle Scholar

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© Kluwer Academic Publishers 1997

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  • I. P. Touw

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