ArticleThe Journal of biological chemistry2013
Induction of a tumor-associated activating mutation in protein tyrosine phosphatase Ptpn11 (Shp2) enhances mitochondrial metabolism, leading to oxidative stress and senescence.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 46 citations in OpenAlex.
- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization.Scientific reports · 2025Article
- SHP2-mediated ROS activation induces chondrocyte paraptosis in osteoarthritis and is attenuated by low-intensity pulsed ultrasound.Journal of orthopaedic translation · 2025Article
- Targeting Shp2 as a therapeutic strategy for neurodegenerative diseases.Translational psychiatry · 2025Review
- The elevation of red blood cell distribution width is an independent prognostic factor for juvenile myelomonocytic leukemia.Blood science (Baltimore, Md.) · 2024Article
- Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes.JCI insight · 2024Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- Macrophage-derived SHP-2 inhibits the metastasis of colorectal cancer via Tie2-PI3K signals.Oncology research · 2023Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Review
- Retinal Src homology region 2-containing protein tyrosine phosphatase 2 silencing alleviates diabetic retinopathy via suppressing inflammatory response and oxidative stress by regulating Yes-associated protein 1 activity.Experimental animals · 2022Article
- Perspectives Regarding the Intersections between STAT3 and Oxidative Metabolism in Cancer.Cells · 2020Review
- Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes.Cancers · 2020Review
- The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life inFrontiers in genetics · 2020Article
- Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells.Oncology letters · 2018Article
- Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduce mitochondrial ROS production.Science signaling · 2017Article
- SHP-2 phosphatase contributes to KRAS-driven intestinal oncogenesis but prevents colitis-associated cancer development.Oncotarget · 2016Article
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
Abstract
Activating mutations in Ptpn11 (Shp2), a protein tyrosine phosphatase involved in diverse cell signaling pathways, are associated with pediatric leukemias and solid tumors. However, the pathogenic effects of these mutations have not been fully characterized. Here, we report that induction of the Ptpn11(E76K/+) mutation, the most common and active Ptpn11 mutation found in leukemias and solid tumors, in primary mouse embryonic fibroblasts resulted in proliferative arrest and premature senescence. As a result, apoptosis was markedly increased. These cellular responses were accompanied and mediated by up-regulation of p53 and p21. Moreover, intracellular levels of reactive oxygen species (ROS), byproducts of mitochondrial oxidative phosphorylation, were elevated in Ptpn11(E76K/+) cells. Since Shp2 is also distributed to the mitochondria (in addition to the cytosol), the impact of the Ptpn11(E76K/+) mutation on mitochondrial function was analyzed. These analyses revealed that oxygen consumption of Ptpn11(E76K/+) cells and the respiratory function of Ptpn11(E76K/+) mitochondria were significantly increased. Furthermore, we found that phosphorylation of mitochondrial Stat3, one of the substrates of Shp2 phosphatase, was greatly decreased in the mutant cells with the activating mutation Ptpn11(E76K/+). This study provides novel insights into the initial effects of tumor-associated Ptpn11 mutations.
Indexed as
Identifiers
What 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.