Thrombopoietin/THPO Products

Description

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 megakaryocytes (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). 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 (15, 16).

Bioinformatics

Uniprot	P40225
Product By Gene ID	7066
Alternate Names	Megakaryocyte colony-stimulating factor Megakaryocyte growth and development factor megakaryocyte stimulating factor MGDF MGDFC-mpl ligand MKCSF MK-CSF ML MPL ligand MPLLG MPLLGMGC163194 Myeloproliferative leukemia virus oncogene ligand THCYT1 THPO thrombopoietin nirs variant 1 Thrombopoietin Tpo TPOMKCSF