ArticleMolecular and cellular biology2000
Role of the distal half of the c-Mpl intracellular domain in control of platelet production by thrombopoietin in vivo.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 51 citations in OpenAlex.
- Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.Leukemia · 2024Article
- Article
- Role of tumor suppressor p53 in megakaryopoiesis and platelet function.Experimental hematology · 2012Article
- Thrombopoietin and hematopoietic stem cells.Cell cycle (Georgetown, Tex.) · 2011Review
- Identification of the residues in the extracellular domain of thrombopoietin receptor involved in the binding of thrombopoietin and a nuclear distribution protein (human NUDC).The Journal of biological chemistry · 2010Article
- Megakaryopoiesis.Seminars in hematology · 2010Review
- Endoreplication: polyploidy with purpose.Genes & development · 2009Review
- An ENU-induced recessive mutation in Mpl leads to thrombocytopenia with overdominance.Experimental hematology · 2009Article
- Signals emanating from the membrane proximal region of the thrombopoietin receptor (mpl) support hematopoietic stem cell self-renewal.Experimental hematology · 2007Article
- Article
- Molecular control of megakaryopoiesis and thrombopoiesis.International journal of hematology · 2002Review
- Dissection of the cytoplasmic domains of cytokine receptors involved in STAT and Ras dependent proliferation.Oncogene · 2002Article
- The molecular and cellular biology of thrombopoietin: the primary regulator of platelet production.Oncogene · 2002Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytokine thrombopoietin (TPO) controls the formation of megakaryocytes and platelets from hematopoietic stem cells. TPO exerts its effect through activation of the c-Mpl receptor and of multiple downstream signal transduction pathways. While the membrane-proximal half of the cytoplasmic domain appears to be required for the activation of signaling molecules that drive proliferation, the distal half and activation of the mitogen-activated protein kinase pathway have been implicated in mediating megakaryocyte maturation in vitro. To investigate the contribution of these two regions of c-Mpl and the signaling pathways they direct in mediating the function of TPO in vivo, we used a knock-in (KI) approach to delete the carboxy-terminal 60 amino acids of the c-Mpl receptor intracellular domain. Mice lacking the C-terminal 60 amino acids of c-Mpl (Delta60 mice) have normal platelet and megakaryocyte counts compared to wild-type mice. Furthermore, platelets in the KI mice are functionally normal, indicating that activation of signaling pathways connected to the C-terminal half of the receptor is not required for megakaryocyte differentiation or platelet production. However, Delta60 mice have an impaired response to exogenous TPO stimulation and display slower recovery from myelosuppressive treatment, suggesting that combinatorial signaling by both ends of the receptor intracellular domain is necessary for an appropriate acute response to TPO.
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