Mouse TPO

Bcakground

Thrombopoietin (Tpo) , is a key regulator of megakaryocytopoiesis and thrombopoiesis. It is principally produced in the liver and is bound and with human and rat Tpo, respectively. It is an 80-85 kDa protein that consists of an N-terminal domain with homology to Erythropoietin (Epo) and a 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 356 amino acid (aa) mouse Tpo precursor is cleaved to yield the 335 aa mature protein. Mature mouse Tpo shares 71% and 81% aa sequence homology C-terminal domain that contains multiple N-linked and O-linked glycosylation sites (4, 5). Tissue specific alternate splicing of mouse 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 (10-12). It is cleaved by platelet-derived thrombin following Arg191 within the C-terminal domain and subsequently at other sites upon extended digestion . 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). Aside from its hematopoietic effects, Tpo is expressed in the brain where it promotes the apoptosis of hypoxia-sensitized neurons and inhibits neuronal differentiation by blocking NGF-induced signaling .

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.

8. 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. VOda, A. et al. (1996) Blood 87:4664.

Specifications

Components and Storage

Quality

SDS-PAGE

Bioactivity

Documents

Mouse TPO