High-Level Expression of Mpl in Platelets and Megakaryocytes Is Independent of Thrombopoietin
| Autor: | William Vainchenker, Karine Cohen-Solal, Natacha Vitrat, Françoise Wendling, Monique Titeux |
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| Rok vydání: | 1999 |
| Předmět: |
Blood Platelets
endocrine system medicine.medical_specialty Transcription Genetic P-selectin medicine.medical_treatment Immunology Platelet Glycoprotein GPIIb-IIIa Complex Biology Proto-Oncogene Mas Biochemistry Mice fluids and secretions Megakaryocyte Proto-Oncogene Proteins Internal medicine medicine Animals Platelet Thrombopoiesis Receptors Cytokine Receptor Cells Cultured Thrombopoietin Megakaryocytopoiesis Growth factor food and beverages hemic and immune systems Cell Biology Hematology Thrombocytopenia Molecular biology Neoplasm Proteins Mice Inbred C57BL P-Selectin medicine.anatomical_structure Endocrinology Mice Inbred DBA embryonic structures Megakaryocytes Receptors Thrombopoietin |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v93.9.2859 |
| Popis: | 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 RNase protection analysis, we found no differences in the levels ofc-mpl transcripts in megakaryocytes (MKs) produced in vitro either in the presence or absence of TPO and in platelets (PLTs) obtained from mice hyperstimulated in vivo by ectopic secretion of TPO. Similarly, Western blot analysis of MKs produced in the presence or absence of TPO showed no difference in Mpl levels. Levels of Mpl, GpIIb, or P-selectin were virtually identical in platelet lysates obtained from normal, TPO knockout and mildly TPO-stimulated mice. In contrast, the expression of Mpl was significantly reduced in PLTs from severely thrombocythemic mice. These results show that TPO does not have a major effect on the transcription or translation of Mpl. However, they do suggest that an excess of circulating TPO can lead to the disappearance of Mpl from PLTs via catabolism. |
| Databáze: | OpenAIRE |
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