ArticleBlood2006
An amphipathic motif at the transmembrane-cytoplasmic junction prevents autonomous activation of the thrombopoietin receptor.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
What it found
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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
68 citing papers in PubMed, 1 synthesis or guideline pooled it.
- JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022Pooled it
- Genomic insights transform diagnosis, prognosis, and therapy in BCR::ABL1-negative myeloproliferative neoplasms.International journal of hematology · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- A Murine Bispecific Antibody Efficiently Redirects T Cells Against Calr Mutated Stem Cells In Vivo.American journal of hematology · 2026Article
- Understanding Triple Negative Myeloproliferative Neoplasms and Identifying Molecular Drivers.Current hematologic malignancy reports · 2026Review
- A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.Nature communications · 2024Article
- Article
- Effects of calreticulin mutations on cell transformation and immunity.Journal of cellular and molecular medicine · 2023Review
- Essential thrombocythaemia progression to the fibrotic phase is associated with a decrease in JAK2 and PDL1 levels.Annals of hematology · 2022Article
- MPL S505C enhances driver mutations at W515 in essential thrombocythemia.Blood cancer journal · 2021Article
- In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021Review
- Integration of Molecular Information in Risk Assessment of Patients with Myeloproliferative Neoplasms.Cells · 2021Review
- Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics.Cancers · 2021Review
- Review
- Disease modifying agents of myeloproliferative neoplasms: a review.Blood research · 2021Review
- LowGenes · 2021Article
- Cytokine receptor splice variants in hematologic diseases.Cytokine · 2020Review
- Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations.Science (New York, N.Y.) · 2020Article
- Recent insights regarding the molecular basis of myeloproliferative neoplasms.The Korean journal of internal medicine · 2020Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Ligand binding to the thrombopoietin receptor (TpoR) is thought to impose a dimeric receptor conformation(s) leading to hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation. Unlike other cytokine receptors, such as the erythropoietin receptor, TpoR contains an amphipathic KWQFP motif at the junction between the transmembrane (TM) and cytoplasmic domains. We show here that a mutant TpoR (delta5TpoR), where this sequence was deleted, is constitutively active. In the absence of ligand, delta5TpoR activates Jak2, Tyk2, STAT5, and mitogen-activated protein (MAP) kinase, but does not appear to induce STAT3 phosphorylation. Delta5TpoR induces hematopoietic myeloid differentiation in the absence of Tpo. In the presence of Tpo, the delta5TpoR mutant appears to enhance erythroid differentiation when compared with the Tpo-activated wild-type TpoR. Strikingly, individual substitution of K507 or W508 to alanine also induces constitutive TpoR activation, indicating that the K and W residues within the amphipathic KWQFP motif are crucial for maintaining the unliganded receptor inactive. These residues may be targets for activating mutations in humans. Such a motif may exist in other receptors to prevent ligand-independent activation and to allow signaling via multiple flexible interfaces.
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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.