Binding and regulation of thrombopoietin to human megakaryocytes.
In: British Journal of Haematology, Jg. 100 (1998-03-15), Heft 4, S. 704-711
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Zugriff:
Thrombopoietin (TPO, c-Mpl ligand) is considered to play an important role in the regulation of megakaryocytopoiesis and platelet production by activating the cytokine receptor c-Mpl. We have examined the binding of 125 I-TPO to the human megakaryocytic cell line, CMK, and to primary human megakaryocytes. Scatchard analysis of TPO binding to its cognate receptor in megakaryocytic cells suggested the existence of a single class of c-Mpl receptors. CMK cells exhibited 1223 receptors per cell with a dissociation constant (K d ) of K d = 223 pM, whereas primary human megakaryocytes exhibited 12 140 receptors per cell and a dissociation constant of K d = 749 pM. The pretreatment of CMK cells and primary bone marrow megakaryocytes with TPO resulted in a decreased binding of TPO to the c-Mpl receptors. This down-regulation was observed within 3 h and was not inhibited by cycloheximide. Phorbol ester, an activator of protein kinase C, also inhibited TPO binding to the c-Mpl receptors by reducing the number of these receptors. The pretreatment of CMK cells with IL-3, IL-6 and DMSO, all of which induced the differentiation of CMK cells, did not affect the binding of TPO to the c-Mpl receptors. These results suggest an additional mechanism, where protein kinase C may help to regulate the binding of TPO to these cells. [ABSTRACT FROM AUTHOR]
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Titel: |
Binding and regulation of thrombopoietin to human megakaryocytes.
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Autor/in / Beteiligte Person: | Sato, Takeyuki ; Fuse, Akira ; Niimi, Hiroo ; Fielder, Paul J. ; Avraham, Hava |
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Zeitschrift: | British Journal of Haematology, Jg. 100 (1998-03-15), Heft 4, S. 704-711 |
Veröffentlichung: | 1998 |
Medientyp: | academicJournal |
ISSN: | 0007-1048 (print) |
DOI: | 10.1046/j.1365-2141.1998.00622.x |
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