Thrombopoietin and its receptor (Mpl) support survival and proliferation in megakaryocyte progenitors and in BaF3 cells engineered to stably express Mpl (BaF3/Mpl). The binding of thrombopoietin to Mpl activates multiple kinase pathways, including the Jak/STAT, Ras/Raf/MAPK, and phosphatidylinositol 3-kinase pathways, but it is not clear how these kinases promote cell cycling. Here, we show tha...

Thrombopoietin (TPO) is the major regulator of both growth and differentiation of megakaryocytes. We previously showed that both functions can be generated by TPO in the megakaryoblastic cell line UT7, in which murine Mpl was introduced, and are independently controlled by distinct regions of the cytoplasmic domain of Mpl. Particularly, residues 71 to 94 of this domain (deleted in the mutant mp...

Mpl ligand (thrombopoietin [TPO]) is the physiological regulator of platelet production. In mice, mRNA encoding the Mpl ligand (Mpl-L) is predominantly found by Northern blot analysis in the liver and kidney. To investigate the mode of regulation of the Mpl-L gene, we have developed several experimental models of severe thrombocytopenia differing in their kinetics and an opposite model of chron...

P ronounced thrombocytosis can result from decreased expression of the thrombopoietin (Tpo) receptor, Mpl, in late megakaryocytes and platelets. In this issue of Blood, Lannutti and colleagues1 and Tiedt and colleagues2 generate transgenic mice expressing Mpl and use these models to investigate the relationships between Mpl, expression and platelet production. In these mouse models, a 2 kb prox...

The chronic myeloproliferative disorders (MPD) are clonal hematopoietic stem cell disorders of unknown etiology. We have reported defective thrombopoietin receptor (Mpl) protein expression in MPD patients. To determine whether the basis of abnormal Mpl protein expression was due to mutations in the Mpl gene, we sequenced Mpl cDNA from MPD patients. We found a single nucleotide substitution (G12...

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to g...

OBJECTIVE The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mu...

Specific lipoxygenase isoforms immunolocalize to the cytosol of a single cell layer in the soybean (Glycine max L.) pod wall. The cells of this layer, termed the mid-pericarp layer (MPL), are larger than adjacent cells and are highly branched. The entire MPL appears to form an elaborate interdigitated network within the pod wall. A particularly striking feature of the MPL is the presence of ext...

In this work, an analytical model of the microporous layer MPL and the catalyst layer CL interface under compression is developed to investigate the effects of the MPL|CL interfacial morphology on the ohmic and mass transport losses at the MPL|CL interface in a polymer electrolyte fuel cell PEFC . The model utilizes experimentally measured surface profile data as input. Results indicate that th...

A mechanism-based model was developed to describe the effects of methylprednisolone (MPL), circadian rhythms, and the glucose/free fatty acid (FFA)/insulin system on leptin and adiponectin expression in white adipose tissue in rats. Fifty-four normal Wistar rats received 50 mg/kg MPL intramuscularly and were sacrificed at various times. An additional set of 54 normal Wistar rats were sacrificed...