Recombinant Mouse TPO, 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 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 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 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

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

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

[12]. VOda, A. et al. (1996) Blood 87:4664.