ArticlePloS one2013
Activating mutations in protein tyrosine phosphatase Ptpn11 (Shp2) enhance reactive oxygen species production that contributes to myeloproliferative disorder.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Association between de novo variants of nuclear-encoded mitochondrial-related genes and undiagnosed developmental disorder and autism.QJM : monthly journal of the Association of Physicians · 2024Article
- SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1.Journal of cell communication and signaling · 2023Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Review
- Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022Review
- New Markers of Disease Progression in Myelofibrosis.Cancers · 2021Review
- Oxidants in Physiological Processes.Handbook of experimental pharmacology · 2021Review
- Activating Mutation of SHP2 Establishes a Tumorigenic Phonotype Through Cell-Autonomous and Non-Cell-Autonomous Mechanisms.Frontiers in cell and developmental biology · 2021Review
- Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model.Frontiers in cell and developmental biology · 2020Article
- DUOXA1-mediated ROS production promotes cisplatin resistance by activating ATR-Chk1 pathway in ovarian cancer.Cancer letters · 2018Article
- Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side.Journal of experimental & clinical cancer research : CR · 2018Review
- SHP2-Mediated Signal Networks in Stem Cell Homeostasis and Dysfunction.Stem cells international · 2018Review
- Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Article
- Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways.Oxidative medicine and cellular longevity · 2016Article
- The Role of Reactive Oxygen Species in Myelofibrosis and Related Neoplasms.Mediators of inflammation · 2015Review
- LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting.Frontiers in oncology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gain of function (GOF) mutations in protein tyrosine phosphatase Ptpn11 have been identified in childhood leukemias, and these mutations are sufficient to drive the development of myeloproliferative disorder and malignant leukemias in mice. However, the molecular mechanisms by which Ptpn11 mutations induce these malignancies are not completely understood. Here we report that Ptpn11 GOF mutations cause cytokine hypersensitivity in hematopoietic cells partly by enhancing the production of reactive oxygen species (ROS). GOF mutations D61G or E76K in Ptpn11 increased ROS levels in myeloid progenitors but not in hematopoietic stem cells. Increased ROS enhanced cellular responses to cytokines by promoting cytokine signaling. Treatment with an antioxidant partially corrected cytokine hypersensitivity in Ptpn11 mutant progenitors. Further analyses demonstrated that Ptpn11 mutations increased mitochondrial aerobic metabolism by interacting with a novel substrate in the mitochondria. This study provides new insights into the pathogenic effects of GOF mutations of Ptpn11 and implies that antioxidants may have a therapeutic benefit for the leukemic patients with these mutations.
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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.