ArticleNature communications2023
Oncogenic CALR mutant C-terminus mediates dual binding to the thrombopoietin receptor triggering complex dimerization and activation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Targeted Next-Generation Sequencing of JAK2, CALR, and MPL in 10 326 Patients With Suspected Myeloproliferative Neoplasm.American journal of hematology · 2026Article
- Resolving diagnostic uncertainty in rare MPL and CALR variants: A practical framework for the haematology clinic.British journal of haematology · 2026Article
- Mutant calreticulin-directed immunotherapies in myeloproliferative neoplasms.Blood neoplasia · 2026Review
- CALR/HIF-1α Positive Feedback Loop Drives CALR Upregulation to Promote EMT-Mediated Bladder Cancer Progression via ROS/AKT Axis.Cancer science · 2026Article
- A Murine Bispecific Antibody Efficiently Redirects T Cells Against Calr Mutated Stem Cells In Vivo.American journal of hematology · 2026Article
- Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis.Blood · 2026Review
- Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms.Journal for immunotherapy of cancer · 2026Article
- CALR accelerates the growth of liver cancer cells by enhancing telomere activity via ARAF.Genes & diseases · 2026Article
- Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms.Cancers · 2025Review
- [The role of AKT inhibitors combined with Ruxolitinib in ameliorating myeloproliferative disorders in mice with CALR gene mutations].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Lessons from Deep Learning Structural Prediction of Multistate Multidomain Proteins-The Case Study of Coiled-Coil NOD-like Receptors.International journal of molecular sciences · 2025Article
- Mutant Calreticulin in MPN: Mechanistic Insights and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- Molecular Profile of BCR-ABL1 Negative Myeloproliferative Neoplasm in a Moroccan Population.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Lysosomal degradation targets mutant calreticulin and the thrombopoietin receptor in myeloproliferative neoplasms.Blood advances · 2024Article
- Structural Modeling of Cytokine-Receptor-JAK2 Signaling Complexes Using AlphaFold Multimer.Journal of chemical information and modeling · 2023Article
- Structural modeling of cytokine-receptor-JAK2 signaling complexes using AlphaFold Multimer.bioRxiv : the preprint server for biology · 2023Article
- Leukemic conversion involvingFrontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calreticulin (CALR) frameshift mutations represent the second cause of myeloproliferative neoplasms (MPN). In healthy cells, CALR transiently and non-specifically interacts with immature N-glycosylated proteins through its N-terminal domain. Conversely, CALR frameshift mutants turn into rogue cytokines by stably and specifically interacting with the Thrombopoietin Receptor (TpoR), inducing its constitutive activation. Here, we identify the basis of the acquired specificity of CALR mutants for TpoR and define the mechanisms by which complex formation triggers TpoR dimerization and activation. Our work reveals that CALR mutant C-terminus unmasks CALR N-terminal domain, rendering it more accessible to bind immature N-glycans on TpoR. We further find that the basic mutant C-terminus is partially α-helical and define how its α-helical segment concomitantly binds acidic patches of TpoR extracellular domain and induces dimerization of both CALR mutant and TpoR. Finally, we propose a model of the tetrameric TpoR-CALR mutant complex and identify potentially targetable sites.
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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 Socratic graph.