TPO, Human, HEK293 Cells,Tag Free

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 Tpo R/c-mpl. Defects in the Tpo-Tpo R 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 alternate 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 in the MK lineage (8, 9). Tpo additionally promotes platelet

production, aggregation, 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 Tpo R or inducing MK growth and differentiation (5). 

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.