Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role during megakaryocytopoiesis. Previously, we have shown that the promoter activity of c-mpl induced by TPO is modulated by transcription through a PKC-dependent pathway and that GATA(-77) is involved as a positive regulatory element in TPO-induced c-mpl gene expression in the megakaryoblastic CMK cells. In this research, to exam...

Monophosphoryl lipid A (MPL) is a nontoxic derivative of lipopolysaccharide (LPS) that exhibits adjuvant properties similar to those of the parent LPS molecule. However, the mechanism by which MPL initiates its immunostimulatory properties remains unclear. Due to the involvement of Toll-like receptors in recognizing and transducing intracellular signals in response to LPS, the aim of the presen...

Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl)...

Using immunohistochemistry, we investigated the expression of c-mpl in bone marrow megakaryocytes of 88 patients with essential thrombocythemia (ET), 6 patients with secondary thrombocytosis (ST), and 20 patients with lymphoma (controls). Considering both the pattern of expression and the staining intensity, we identified a uniform and a heterogeneous pattern of c-mpl expression. The uniform pa...

Using immunohistochemistry, we investigated the expression of c-mpl in bone marrow megakaryocytes of 88 patients with essential thrombocythemia (ET), 6 patients with secondary thrombocytosis (ST), and 20 patients with lymphoma (controls). Considering both the pattern of expression and the staining intensity, we identified a uniform and a heterogeneous pattern of c-mpl expression. The uniform pa...

Similar to two other hematopoietic growth factor receptors, the c-fms (macrophage colony-stimulating factor receptor) and the c-kit genes, c-mpl has been discovered through the study of oncogenic retroviruses. Unlike c-fms and c-kit, which both belong to a subgroup of tyrosine kinase receptors, the c-mpl proto-oncogene encodes a new member of the cytokine receptor superfamily. We have studied t...

The thrombopoietin receptor, Mpl, is a member of the cytokine receptor superfamily. The extracellular domain of Mpl contains two copies of the cytokine receptor homology module (CRM). Mpl is encoded by c-mpl, the cellular homologue of the oncogene v-mpl. The oncogenic potential of v-mpl may arise from deletion of all but the 43 most membrane-proximal amino acids of the extracellular domain of t...

NIP-004 is a novel synthetic compound developed to display human thrombopoietin (TPO) receptor (c-Mpl) agonist activity. NIP-004 displays species specificity, stimulating proliferation or differentiation of human c-Mpl-expressing cells such as UT-7/TPO and human CD34(+) cells but not murine c-Mpl-expressing cells or cynomolgus monkey cells. To test the mechanism of its action, we constructed mu...

Monophosphoryl lipid A (MPL) is a non-toxic TLR4 ligand, derived from Salmonella minnesota R595 (Re) lipopolysaccharide (LPS) by chemical modification. It is clinically used as an adjuvant for cancer treatment (Fendrix, Ceravix) and allergen specific immunotherapy (Pollinex Quattro, ORALVAC). Nevertheless, reports on the mechanism of adjuvant activity are limited. The aim of this study was to c...

Thrombopoietin (TPO) is a hematopoietic growth factor that regulates megakaryocytopoiesis and platelet production through binding to its receptor, Mpl, encoded by the c-mpl proto-oncogene. Circulating levels of TPO are regulated by receptor-mediated uptake and degradation. To better understand this mode of TPO regulation, we examined whether expression of Mpl was regulated by its ligand. Using ...