ArticleMolecular and cellular biology1996
Functional regions of the mouse thrombopoietin receptor cytoplasmic domain: evidence for a critical region which is involved in differentiation and can be complemented by erythropoietin.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 88 citations in OpenAlex.
- Hematopoietic niche drives FLT3-ITD acute myeloid leukemia resistance to quizartinibHaematologica · 2019Trial
- Mpl traffics to the cell surface through conventional and unconventional routes.Traffic (Copenhagen, Denmark) · 2014Article
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- Orientation-specific signalling by thrombopoietin receptor dimers.The EMBO journal · 2011Article
- A senescence-like cell-cycle arrest occurs during megakaryocytic maturation: implications for physiological and pathological megakaryocytic proliferation.PLoS biology · 2010Article
- OTT-MAL is a deregulated activator of serum response factor-dependent gene expression.Molecular and cellular biology · 2008Article
- Cytokine receptors and hematopoietic differentiation.Oncogene · 2007Review
- Article
- Selective modification of eukaryotic initiation factor 4F (eIF4F) at the onset of cell differentiation: recruitment of eIF4GII and long-lasting phosphorylation of eIF4E.Molecular and cellular biology · 2004Article
- STAT5 and Oct-1 form a stable complex that modulates cyclin D1 expression.Molecular and cellular biology · 2003Article
- 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
- Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo).Oncogene · 2001Article
- Structural and functional hot spots in cytokine receptors.International journal of hematology · 2001Review
- Thrombopoietin-mediated sustained activation of extracellular signal-regulated kinase in UT7-Mpl cells requires both Ras-Raf-1- and Rap1-B-Raf-dependent pathways.Molecular and cellular biology · 2001Article
- Biogenesis of endoplasmic reticulum proteins involved in Ca2+ signalling during megakaryocytic differentiation: an in vitro study.The Biochemical journal · 2000Article
- A new feature of Mpl receptor: ligand-induced transforming activity in FRE rat fibroblasts.Oncogene · 2000Article
- Design of conditionally active STATs: insights into STAT activation and gene regulatory function.Molecular and cellular biology · 1999Article
- Article
- Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. To identify functionally important regions in the cytoplasmic domain of the TPO receptor, mpl, we introduced wild-type mpl and deletion mutants of murine mpl into the granulocyte-macrophage colony-stimulating factor (GM-CSF)- or erythropoietin (EPO)-dependent human cell line UT7. TPO induced differentiation of UT7-Wtmpl cells, not parental UT7 cells, along the megakaryocytic lineage, as evidenced by decreased proliferation, changes in cell morphology, and increased surface expression and mRNA levels of megakaryocytic markers CD41, CD61, and CD42b. When UT7-mpl cells were cultured long-term in EPO instead of GM-CSF, the TPO effect was dominant over that of EPO. Moreover, the differentiation induced by TPO was more pronounced for cells shifted from EPO to TPO than for cells shifted from GM-CSF to TPO, as shown by the appearance of polyploid cells. Mutational analysis of the cytoplasmic domain of mpl showed that proliferation and maturation functions of mpl can be uncoupled. Two functional regions were identified: (i) the first 69 amino acids comprising the cytokine receptor motifs, box I and box 2, which are necessary for both TPO-induced mitogenesis and maturation; and (ii) amino acids 71 to 94, which are dispensable for proliferation but required for differentiation. Surprisingly, however, EPO could complement this latter domain for TPO-induced differentiation, suggesting a close relationship between EPO and TPO signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.