ArticleThe EMBO journal2019
PTPN3 acts as a tumor suppressor and boosts TGF-β signaling independent of its phosphatase activity.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- SHP2 negatively regulates TGF-β signaling by destabilizing the TGF-β type I receptor.Cell communication and signaling : CCS · 2026Article
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- Multiomic analysis of clonal development reveals new regulators of leukemic cell growth.Genes & development · 2026Article
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- Retinol saturase promotes tubulointerstitial fibrosis in diabetic kidney disease by inhibiting ChREBP ubiquitination via Smurf2 suppression.Frontiers in endocrinology · 2026Article
- Harnessing Tumor Cell-Derived Exosomes for Immune Rejection Management in Corneal Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- AMDHD1 acts as a tumor suppressor and contributes to activation of TGF-β signaling pathway in cholangiocarcinoma.Cell death and differentiation · 2025Article
- Targeting the dual miRNA/BMP2 network: LncRNA H19-mediated temozolomide resistance unveils novel therapeutic strategies in glioblastoma.Frontiers in oncology · 2025Article
- Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling.Biomolecules · 2024Review
- Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.ACS omega · 2024Article
- Review
- Tea domain transcription factor TEAD4 mitigates TGF-β signaling and hepatocellular carcinoma progression independently of YAP.Journal of molecular cell biology · 2023Article
- Imatinib blocks tyrosine phosphorylation of Smad4 and restores TGF-β growth-suppressive signaling in BCR-ABL1-positive leukemia.Signal transduction and targeted therapy · 2023Article
- PTPN3 in cancer: unveiling its immune-mediated impact on prognosis and dysregulated signaling pathways.American journal of translational research · 2023Article
- Novel Potential Therapeutic Targets of PTPN Families for Lung Cancer.Journal of personalized medicine · 2022Article
- Review
- PTPN3 acts as a tumor suppressor and boosts TGF-β signaling independent of its phosphatase activity.The EMBO journal · 2019Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
TGF-β controls a variety of cellular functions during development. Abnormal TGF-β responses are commonly found in human diseases such as cancer, suggesting that TGF-β signaling must be tightly regulated. Here, we report that protein tyrosine phosphatase non-receptor 3 (PTPN3) profoundly potentiates TGF-β signaling independent of its phosphatase activity. PTPN3 stabilizes TGF-β type I receptor (TβRI) through attenuating the interaction between Smurf2 and TβRI. Consequently, PTPN3 facilitates TGF-β-induced R-Smad phosphorylation, transcriptional responses, and subsequent physiological responses. Importantly, the leucine-to-arginine substitution at amino acid residue 232 (L232R) of PTPN3, a frequent mutation found in intrahepatic cholangiocarcinoma (ICC), disables its role in enhancing TGF-β signaling and abolishes its tumor-suppressive function. Our findings have revealed a vital role of PTPN3 in regulating TGF-β signaling during normal physiology and pathogenesis.
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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.