ArticleMolecular and cellular biology1997
Control of thrombopoietin-induced megakaryocytic differentiation by the mitogen-activated protein kinase pathway.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 149 citations in OpenAlex.
- Recombinant human thrombopoietin for chronic liver disease-associated thrombocytopenia with or without concomitant infections: a real-world retrospective study.Frontiers in pharmacology · 2026Article
- Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome.Acta biochimica et biophysica Sinica · 2025Article
- A Novel Antithrombocytopenia Agent,International journal of molecular sciences · 2022Article
- Thrombocytopenia in chronic liver disease: Physiopathology and new therapeutic strategies before invasive procedures.World journal of gastroenterology · 2022Review
- Identification of Modulators of HIV-1 Proviral Transcription from a Library of FDA-Approved Pharmaceuticals.Viruses · 2020Article
- Article
- CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.Journal of cancer research and clinical oncology · 2019Article
- Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex vivo expanded haematopoietic stem cells.Journal of cellular and molecular medicine · 2018Article
- Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis.Scientific reports · 2017Article
- Thrombin Maybe Plays an Important Role in MK Differentiation into Platelets.BioMed research international · 2016Article
- Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia.OncoTargets and therapy · 2016Article
- The pathophysiology of thrombocytopenia in chronic liver disease.Hepatic medicine : evidence and research · 2016Review
- JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation.Blood · 2014Article
- Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation.The Journal of clinical investigation · 2014Article
- Article
- PSTPIP2 dysregulation contributes to aberrant terminal differentiation in GATA-1-deficient megakaryocytes by activating LYN.Cell death & disease · 2014Article
- Effects of radiation on the maturation of megakaryocytes.Journal of radiation research · 2013Article
- Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate.Journal of radiation research · 2013Article
- Crosstalk between the Smad and the Mitogen-Activated Protein Kinase Pathways is Essential for Erythroid Differentiation of Erythroleukemia Cells Induced by TGF-β, Activin, Hydroxyurea and Butyrate.Journal of leukemia (Los Angeles, Calif.) · 2013Article
- Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases.Journal of hematology & oncology · 2013Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombopoietin (TPO) is the major regulator of both growth and differentiation of megakaryocytes. We previously showed that both functions can be generated by TPO in the megakaryoblastic cell line UT7, in which murine Mpl was introduced, and are independently controlled by distinct regions of the cytoplasmic domain of Mpl. Particularly, residues 71 to 94 of this domain (deleted in the mutant mpl delta3) were found to be required for megakaryocytic maturation but dispensable for proliferation. We show here that TPO-induced differentiation in UT7 cells is tightly dependent on a strong, long-lasting activation of the mitogen-activated protein kinase (MAPK) pathway. Indeed, (i) in UT7-mpl cells, TPO induced a strong activation of extracellular signal-regulated kinases (ERK) which was persistent until at least 4 days in TPO-containing medium; (ii) a specific MAPK kinase (MEK) inhibitor inhibited TPO-induced megakaryocytic gene expression; (iii) the Mpl mutant mpl delta3, which displayed no maturation activity, transduced only a weak and transient ERK activation in UT7 cells; and (iv) TPO-induced megakaryocytic differentiation in UT7-mpl delta3 cells was partially restored by expression of a constitutively activated mutant of MEK. The capacity of TPO to trigger a strong and prolonged MAPK signal depended on the cell in which Mpl was introduced. In BAF3-mpl cells, TPO triggered a weak and transient ERK activation, similar to that induced in UT7-mpl delta3 cells. In these cells, no difference in MAPK activation was found between normal Mpl and mpl delta3. Thus, depending on the cellular context, several distinct regions of the cytoplasmic domain of Mpl and signaling pathways may contribute to generate quantitative variations in MAPK activation.
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