Defects in the Tpo‑Tpo R signaling pathway are associated with a variety of platelet disorders. 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. Tissue specific alternate splicing of human Tpo generates multiple isoforms with internal deletions, insertions, and/or C‑terminal substitutions. Tpo promotes the differentiation, proliferation, and maturation of MK and their progenitors. Several other cytokines can promote these functions as well but only in cooperation with Tpo. Notably, IL‑3 independently induces MK development, although its effects are restricted to early in the MK lineage. Tpo additionally promotes platelet production, aggregation, ECM adhesion, and activation. 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. The C‑terminal domain is not required for binding to Tpo R or inducing MK growth and differentiation. 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.
>97%, by SDS-PAGE with silver staining
Lyophilized from a 0.2 μm filtered solution in Acetonitrile and TFA with BSA as a carrier protein.
Measured in a cell proliferation assay using MO7e human megakaryocytic leukemic cells. Avanzi, G. et al. (1988) Br. J. Haematol. 69:359. The ED50 for this effect is 0.3-3 ng/mL.
Reconstitute at 50-200 μg/mL in sterile 4 mM HCl containing at least 0.1% human or bovine serum albumin.
Tpo promotes platelet production, aggregation, ECM adhesion, and activation.
Examples of Clinical Use:
Promoting platelet production, aggregation, ECM adhesion, and activation.
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