Recombinant Human Thrombopoietin/TPO (His, Flag)

Thrombopoietin (Tpo) is a key regulator of megakaryopoiesis and thrombosis. It is mainly produced in the liver and is bound and internalized by the receptor Tpo R/c-mpl. Defects in the Tpo-Tpo-R signaling pathway have been implicated in a variety of platelet disorders. The 353-amino acid (aa) human Tpo precursor is cleaved to produce a 332-amino acid mature protein. Mature human Tpo has approximately 70% aa sequence homology with mouse and rat Tpo. It is an 80-85 kDa protein consisting of an N-terminal domain homologous to erythropoietin (Epoietin) and a C-terminal domain containing multiple N-linked and O-linked glycosylation sites. Tissue-specific alternating splicing of human Tpo yields multiple isoforms with internal deletions, insertions, and/or C-terminal substitutions. Tpo promotes the differentiation, proliferation, and maturation of MK and its progenitor cells. Several other cytokines can also promote these functions, but only synergistically with Tpo. Notably, IL-3 independently induces MK development, although its effects are limited to the early stages of the MK lineage. TPO also promotes platelet production, aggregation, ECM adhesion, and activation. Following Arg191 within the C-terminal domain, it is cleaved by platelet-derived thrombin and subsequently cleaved at other sites upon extended digestion. Full-length Tpo and shorter forms are circulated in the plasma. A C-terminal domain is not required for binding Tpo R or inducing MK growth and differentiation.