ArticleThe EMBO journal1996
Tyrosine-599 of the c-Mpl receptor is required for Shc phosphorylation and the induction of cellular differentiation.
Article in The EMBO journal, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 90 citations in OpenAlex.
- Thrombopoietin increases susceptibility for EVI1 + KMT2A-MLLT3-driven AML expressing stem cell genes linked to poor outcome.Nature communications · 2025Article
- Elevated 5-HTR7 deteriorates dysregulated megakaryocytopoiesis in immune thrombocytopenic purpura via upregulating the PKA/Orai1/ERK1/2 pathway.Haematologica · 2025Article
- Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.Leukemia · 2024Article
- Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.Frontiers in oncology · 2022Article
- Cytokine receptor splice variants in hematologic diseases.Cytokine · 2020Review
- The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.Frontiers in endocrinology · 2017Review
- Article
- C-Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis.Journal of cellular biochemistry · 2016Article
- Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms.Cell & bioscience · 2016Article
- PSTPIP2 dysregulation contributes to aberrant terminal differentiation in GATA-1-deficient megakaryocytes by activating LYN.Cell death & disease · 2014Article
- Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases.Journal of hematology & oncology · 2013Review
- Live-cell visualization of intracellular interaction between a nuclear migration protein (hNUDC) and the thrombopoietin receptor (Mpl).PloS one · 2012Article
- Orientation-specific signalling by thrombopoietin receptor dimers.The EMBO journal · 2011Article
- Megakaryopoiesis.Seminars in hematology · 2010Review
- Article
- Towards predictive models of stem cell fate.Cytotechnology · 2003Article
- Article
- Molecular control of megakaryopoiesis and thrombopoiesis.International journal of hematology · 2002Review
- The molecular and cellular biology of thrombopoietin: the primary regulator of platelet production.Oncogene · 2002Review
- Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo).Oncogene · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interaction of thrombopoietin (TPO) with its receptor, c-Mpl, triggers cell growth and differentiation responses controlling primitive haemopoietic cell production and megakaryocytopoiesis. To examine the important receptor domains and signal transduction pathways involved in these cellular responses, c-Mpl cytoplasmic domain truncation and tyrosine substitution mutants were generated. In the myelomonocytic leukaemia cell lines WEHI3B-D+ and M1, ectopic expression of the wild-type c-Mpl receptor induced TPO-dependent cellular differentiation characterized by increased cell migration through agar and acquisition of the morphology and molecular markers of macrophages. Consistent with the concept that proliferative and differentiation signals emanate from distinct receptor domains, the C-terminal 33 amino acids of c-Mpl were dispensable for a proliferative response in Ba/F3 cells but proved critical for WEHI3B-D+ and M1 differentiation. Finer mapping revealed that substitution of Tyr599 by phenylalanine within this c-Mpl domain was sufficient to abolish the normal differentiation response. Moreover, in contrast to the normal c-Mpl receptor, this same mplY599F mutant was also incapable of stimulating TPO-dependent Shc phosphorylation, the association of Shc with Grb2 or c-Mpl and of inducing c-fos expression. Thus activation of components of the Ras signalling cascade, initiated by interaction of Shc with c-Mpl Tyr599, may play a decisive role in specific differentiation signals emanating from the c-Mpl receptor.
Indexed as
Identifiers
8978680PMC452478W869346529What OpenQuestion holds
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.