PMID: 9531337Apr 8, 1998Paper

Binding and regulation of thrombopoietin to human megakaryocytes

British Journal of Haematology
T SatoH Avraham

Abstract

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 125I-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 (Kd) of Kd = 223 pM, whereas primary human megakaryocytes exhibited 12140 receptors per cell and a dissociation constant of Kd = 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, whe...Continue Reading

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Citations

Dec 20, 2012·Pharmaceutical Research·Wojciech KrzyzanskiYow-Ming Wang
Aug 30, 2000·Early Human Development·N A MurrayI A Roberts
Mar 29, 2000·The International Journal of Biochemistry & Cell Biology·D P HsiehP P Xu
Aug 24, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·F HeitsW Jelkmann
Feb 20, 2010·Okajimas Folia Anatomica Japonica·Masataka SunoharaIwao Sato
Dec 24, 2010·Okajimas Folia Anatomica Japonica·Masataka SunoharaIwao Sato
Aug 21, 2013·Journal of Cellular Biochemistry·Christopher J Carbone, Serge Y Fuchs
Oct 4, 2002·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Ibrahim C HaznedarogluMustafa Benekli
Apr 12, 2018·Physiology·Fred G Pluthero, Walter H A Kahr
Jul 28, 2001·European Journal of Gastroenterology & Hepatology·W Jelkmann
Apr 26, 2013·Okajimas Folia Anatomica Japonica·Masataka SunoharaIwao Sato
May 13, 2014·Okajimas Folia Anatomica Japonica·Masataka SunoharaIwao Sato

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