Human TPO

Bcakground

Thrombopoietin (Tpo) is a key regulator of megakaryocytopoiesis and thrombopoiesis. It is principally produced in the liver and is bound and internalized by the receptor TpoR/c-Mpl. Defects in the Tpo–TpoR signaling pathway are associated with a variety of platelet disorders (1–3).

The 353 amino acid (aa) human Tpo precursor is cleaved to yield the 332 aa mature protein. Mature human Tpo shares approximately 70% aa sequence homology with mouse and rat Tpo. It is an 80–85 kDa protein that consists of an N-terminal domain with homology to erythropoietin (Epo) and a C-terminal domain that contains multiple N-linked and O-linked glycosylation sites (4, 5).

Tissue-specific alternative splicing of human Tpo generates multiple isoforms with internal deletions, insertions, and/or C-terminal substitutions (6). Tpo promotes the differentiation, proliferation, and maturation of MK and their progenitors (4, 5, 7). Several other cytokines can promote these functions as well, but only in cooperation with Tpo (8, 9). Notably, IL-3 independently induces MK development, although its effects are restricted to early stages in the MK lineage (8, 9).

Tpo additionally promotes platelet production, aggregation, extracellular matrix (ECM) adhesion, and activation (10, 13). It is cleaved by platelet-derived thrombin following Arg191 within the C-terminal domain and subsequently at other sites upon extended digestion (14). Full-length Tpo and shorter forms circulate in the plasma (4, 5). The C-terminal domain is not required for binding to TpoR or inducing MK growth and differentiation (5).

Reference

1. Deutsch, V.R. and A. Tomer (2006) Br. J. Haematol. 134:453.

2. Kaushansky, K. (2005) J. Clin. Invest. 115:3339.

3. Li, J. et al. (1999) Br. J. Haematol. 106:345.

4. Bartley, T.D. et al. (1994) Cell 77:1117.

5. de Sauvage, F.J. et al. (1994) Nature 369:533.

6. Marcucci, R. and M. Romano (2008) Biochim. Biophys. Acta 1782:427.

7. Kaushansky, K. et al. (1994) Nature 369:568.

8. Kaushansky, K. et al. (1995) Proc. Natl. Acad. Sci. 92:3234.

9. Broudy, V.C. et al. (1995), Blood 85:1719.

10. Lok, S.I. et al. (1994) Nature 369:565.

11. Chen, J. et al. (1995) Blood 86:4054.

12. Oda, A. et al. (1996) Blood 87:4664.

13. Van Os, E. et al. (2003) Br. J. Haematol. 121:482.

14. Kato, T. et al. (1997) Proc. Natl. Acad. Sci. 94:4669.

Specifications

Components and Storage

Quality

SDS-PAGE

Gel filtration

Bioactivity

Documents

Human TPO