ArticleiScience2020
PTPRA Phosphatase Regulates GDNF-Dependent RET Signaling and Inhibits the RET Mutant MEN2A Oncogenic Potential.
Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
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- Transcriptomic Dysregulation in Animal Models of Attention-Deficit Hyperactivity Disorder and Nicotine Dependence Suggests Shared Neural Mechanisms.Brain and behavior · 2025Article
- Extreme-Phenotype Genome-Wide Association Analysis for Growth Traits in Spotted Sea Bass (Animals : an open access journal from MDPI · 2024Article
- Development and validation of a novel high-performance liquid chromatography (HPLC) method for the detection of related substances of pralsetinib, a new anti-lung cancer drug.Frontiers in chemistry · 2024Article
- A network map of GDNF/RET signaling pathway in physiological and pathological conditions.Journal of cell communication and signaling · 2023Article
- GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1.BMC cancer · 2023Article
- Article
- GDNF Receptor Agonist Alleviates Motor Imbalance in Unilateral 6-Hydroxydopamine Model of Parkinson's Disease.Frontiers in neurology and neuroscience research · 2020Article
- Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson's disease.Cell and tissue research · 2020Review
- RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer.International journal of molecular sciences · 2020Review
- Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration.International journal of molecular sciences · 2020Review
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RET proto-oncogene encodes receptor tyrosine kinase, expressed primarily in tissues of neural crest origin. De-regulation of RET signaling is implicated in several human cancers. Recent phosphatome interactome analysis identified PTPRA interacting with the neurotrophic factor (GDNF)-dependent RET-Ras-MAPK signaling-axis. Here, by identifying comprehensive interactomes of PTPRA and RET, we reveal their close physical and functional association. The PTPRA directly interacts with RET, and using the phosphoproteomic approach, we identify RET as a direct dephosphorylation substrate of PTPRA both in vivo and in vitro. The protein phosphatase domain-1 is indispensable for the PTPRA inhibitory role on RET activity and downstream Ras-MAPK signaling, whereas domain-2 has only minor effect. Furthermore, PTPRA also regulates the RET oncogenic mutant variant MEN2A activity and invasion capacity, whereas the MEN2B is insensitive to PTPRA. In sum, we discern PTPRA as a novel regulator of RET signaling in both health and cancer.
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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.