Skip to main content
SpringerLink
Log in

Structure of Thrombopoietin and the Thrombopoietin Gene

  • Chapter
Thrombopoiesis and Thrombopoietins

Abstract

The cloning of thrombopoietin (TPO) has been a significant advance for several fields of scientific inquiry. In addition to enabling the production of recombinant TPO, the cloning of TPO cDNA also facilitates examination of TPO itself, a hemopoietic cytokine with unique structural features. Furthermore, the cloning of the TPO gene enables analysis of the mechanisms by which TPO activity is controlled and homeostasis of the platelet is maintained. This chapter summarizes the current understanding of the structure of TPO and the TPO gene.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. de Sauvage FJ, Hass PE, Spencer SD, et al. Stimulation of megakaryocytopoiesis and throm-bopoiesis by the c-mpl ligand. Nature. 1994; 369: 533–538.

    Article  PubMed  Google Scholar 

  2. Bartley TD, Bogenberger J, Hunt P, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor mpl. Cell. 1994; 77: 1117–1124.

    Article  PubMed  CAS  Google Scholar 

  3. Li B, Dai W. Thrombopoietin and neurotrophins share a common domain. Blood. 1995; 86: 1643–1644.

    PubMed  CAS  Google Scholar 

  4. Lok S, Kaushansky K, Holly RD, et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature. 1994; 369: 565–568.

    Article  PubMed  CAS  Google Scholar 

  5. Narhi LO, Arakawa T, Aoki KH, et al. The effect of carbohydrate on the structure and stability of erythropoietin. J Biol Chem. 1991; 266: 23,022–23,026.

    Google Scholar 

  6. Spivak JL, Hogans BB. The in vivo metabolism of recombinant human erythropoietin in the rat. Blood. 1989; 73: 90–99.

    PubMed  CAS  Google Scholar 

  7. Takeuchi M, Takasaki S, Shimada M, Kobata A. Role of sugar chains in the in vitro biological activity of human erythropoietin produced in recombinant Chinese hamster ovary cells. J Biol Chem. 1990; 265: 12,127–12,130.

    CAS  Google Scholar 

  8. Hunt P, Li Y-S, Nichol JL, et al. Purification and biologic characterization of plasma-derived megakaryocyte growth and development factor. Blood. 1995; 86: 540–547.

    PubMed  CAS  Google Scholar 

  9. Kuter DJ, Beeler DL, Rosenberg RD. The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production. Proc Natl Acad Sci USA. 1994; 91: 11,104–11,108.

    Google Scholar 

  10. Gurney AL, Kuang W-J, Xie M-H, Malloy BE, Eaton DL, de Sauvage F J. Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin. Blood. 1995; 85: 981–988.

    PubMed  CAS  Google Scholar 

  11. Bazan JF. Haemopoietic receptors and helical cytokines. Immunol Today. 1990; 11: 350–354.

    Article  PubMed  CAS  Google Scholar 

  12. Kato T, Ozawa T, Muto T, et al. Essential structure for biological activity of thrombopoietin. Blood. 1995; 86: 365a (abstract no 1448).

    Google Scholar 

  13. Linden H, O’Rork C, Hart CE, et al. The structural and functional role of disulfide bonding in thrombopoietin. Blood. 1995; 86: 255a (abstract no 1008).

    Google Scholar 

  14. Wada T, Nagata Y, Nagahisa H, et al. Characterization of the truncated thrombopoietin variants. Biochem Biophys Res Commun. 1995; 213: 1091–1098.

    Article  PubMed  CAS  Google Scholar 

  15. Chang MS, McNinch J, Basu R, et al. Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene. J Biol Chem. 1995; 270: 511–514.

    Article  PubMed  CAS  Google Scholar 

  16. Nagata S, Tsuchiya M, Asano S, et al. The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor. EMBO J. 1986; 5: 575–581.

    PubMed  CAS  Google Scholar 

  17. Boissel JP, Lee WR, Presnell SR, Cohen FE, Bunn HF. Erythropoietin structure-function relationships. Mutant proteins that test a model of tertiary structure. J Biol Chem. 1993; 268: 15,983–15,993.

    CAS  Google Scholar 

  18. Stoffel R, Wiestner A, Skoda RC. Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mrna level and for a direct regulatory role of platelets. Blood. 1996; 87: 567–573.

    PubMed  CAS  Google Scholar 

  19. Sohma Y, Akahori H, Seki N, et al. Molecular cloning and chromosomal localization of the human thrombopoietin gene. FEBS Lett. 1994; 353: 57–61.

    Article  PubMed  CAS  Google Scholar 

  20. Foster DC, Sprecher CA, Grant FJ, et al. Human thrombopoietin: Gene structure, cDNA sequence, expression, and chromosomal localization. Proc Natl Acad Sci USA. 1994; 91: 13,023–13,027.

    Article  Google Scholar 

  21. McCarty JM, K Kaushansky. Functional charaterization of the thrombopoietin promoter. Blood. 1995; 86: 364a (abstract no 1446).

    Google Scholar 

  22. Ogami K, Kawagishi M, Kudo Y, Kato T, Miyazaki HK, Kawamura K. Promoter analysis and transcriptional regulation of the human thrombopoietin gene. Blood. 1995; 86: 365a (abstract no 1447).

    Google Scholar 

  23. Fielder PJ, Gurney AL, Stefanich E, et al. Regulation of thrombopoietin levels by c-mpl mediated binding to platelets. Blood. 1996; 87: 2154–2161.

    PubMed  CAS  Google Scholar 

  24. McCarty JM, Sprugel KH, Fox NE, Sabath DE, Kaushansky K. Murine thrombopoietin mRNA levels are modulated by platelet count. Blood. 1995; 86: 3668–3675.

    PubMed  CAS  Google Scholar 

  25. de Sauvage FJ, Carver-Moore K, Luoh S-H, et al. Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin. J Exp Med. 1996; 183: 651–656.

    Article  PubMed  Google Scholar 

  26. Pintado T, Ferro MT, San Ramon C, Mayayo M, Larana JG. Clinical correlations of the 3q21; q26 cytogenic anomaly. A leukemic or mylodysplastic syndromewith preserved or increased platelet production and lack of response to cytotoxic drug therapy. Cancer. 1985; 55: 535–541.

    Article  PubMed  CAS  Google Scholar 

  27. Rowley JD, Potter D. Chromosomal banding patterms in acute nonlymphocytic leukemia. Blood. 1976; 47: 705–721.

    PubMed  CAS  Google Scholar 

  28. Jenkins RB, Tefferi A, Solberg LA, Jr, Dewald GW. Acute leukemia with abnormal thrombopoiesis and inversions of chromosome 3. Cancer Genet Cytogenet. 1989; 39: 167–179.

    Article  PubMed  CAS  Google Scholar 

  29. Pinto MR, King MA, Goss GD, et al. Acute megakaryoblastic leukaemia with 3q inversion and elevated thrombopoietin (TSF): an autocrine role for TSF? Br J Haematol. 1985; 61: 687–694.

    Article  PubMed  CAS  Google Scholar 

  30. Suzukawa K, Satoh H, Taniwaki M, Yokota J, Morishita K. The human thrombopoietin gene is located on chromosome 3q26.33-q27, but is not transcriptionally activated in leukemia cells with 3q21 and 3q26 abnormalities (3q21q26 syndrome). Leukemia. 1995; 9: 1328–1331.

    PubMed  CAS  Google Scholar 

  31. Barlow DP, Bucan M, Lehrach H, Hogan BL, Gough NM. Close genetic and physical linkage between the murine haematopoietic growth factor genes GM-CSF and multi-CSF (IL-3). EMBO J. 1987; 6: 617–623.

    PubMed  CAS  Google Scholar 

  32. van Leeuwen BH, Martinson ME, Webb GC, Young IG. Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5. Blood. 1989; 73: 1142–1148.

    PubMed  Google Scholar 

Download references

Authors
  1. Austin L. Gurney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frederic J. de Sauvage
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA

    David J. Kuter MD, DPhil

  2. Amgen Inc., Thousand Oaks, California, USA

    Pamela Hunt PhD  & William Sheridan MD  & 

  3. Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA

    William Sheridan MD

  4. Department of Medicine, New York University Medical Center, New York, New York, USA

    Dorothea Zucker-Franklin MD

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Humana Press Inc.

About this chapter

Cite this chapter

Gurney, A.L., de Sauvage, F.J. (1997). Structure of Thrombopoietin and the Thrombopoietin Gene. In: Kuter, D.J., Hunt, P., Sheridan, W., Zucker-Franklin, D. (eds) Thrombopoiesis and Thrombopoietins. Humana Press. https://doi.org/10.1007/978-1-4612-3958-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-3958-1_11

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-8440-6

  • Online ISBN: 978-1-4612-3958-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation