ArticleMolecular and cellular biology2006
Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin's transcriptional activity.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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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.
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Who cites it
58 citing papers in PubMed, 108 citations in OpenAlex.
- Recurrent mutations in protein tyrosine phosphatase receptor-type kappa in depressed-type colorectal carcinomas.Journal of biochemistry · 2026Article
- Receptor Protein Tyrosine Phosphatases (RPTPs): Structure and Biological Roles in Cancer.Kinases and phosphatases · 2026Article
- Synaptic and Non-Synaptic Functions of PTPRD: A Receptor Tyrosine Phosphatase at the Crossroads of Neural Circuitry and Metabolism.Journal of neurochemistry · 2025Review
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Protein tyrosine phosphatase receptor type kappa (PTPRK) revisited: evolving insights into structure, function, and pathology.Journal of translational medicine · 2025Review
- Review
- PTPRK regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity.Nature communications · 2024Article
- The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.Journal of cell science · 2024Article
- Manipulating PTPRD function with ectodomain antibodies.Genes & development · 2023Article
- Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Frontiers in cell and developmental biology · 2023Review
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Protein Tyrosine Phosphatases: A new paradigm in an old signaling system?Advances in cancer research · 2021Review
- A 14-Marker Multiplexed Imaging Panel for Prognostic Biomarkers and Tumor Heterogeneity in Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Article
- Modulation of Immune Responses by Platelet-Derived ADAM10.Frontiers in immunology · 2020Review
- PTPRM, a candidate tumor suppressor gene in small intestinal neuroendocrine tumors.Endocrine connections · 2019Article
- PTPRK suppresses progression and chemo-resistance of colon cancer cells via direct inhibition of pro-oncogenic CD133.FEBS open bio · 2019Article
- Article
- Clinical significance of ADAM10 expression in laryngeal carcinoma.Oncology letters · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several receptor protein tyrosine phosphatases (RPTPs) are cell adhesion molecules involved in homophilic interactions, suggesting that RPTP outside-in signaling is coupled to cell contact formation. However, little is known about the mechanisms by which cell density regulates RPTP function. We show that the MAM family prototype RPTPkappa is cleaved by three proteases: furin, ADAM 10, and gamma-secretase. Cell density promotes ADAM 10-mediated cleavage and shedding of RPTPkappa. This is followed by gamma-secretase-dependent intramembrane proteolysis of the remaining transmembrane part to release the phosphatase intracellular portion (PIC) from the membrane, thereby allowing its translocation to the nucleus. When cells were treated with leptomycin B, a nuclear export inhibitor, PIC accumulated in nuclear bodies. PIC is an active protein tyrosine phosphatase that binds to and dephosphorylates beta-catenin, an RPTPkappa substrate. The expression of RPTPkappa suppresses beta-catenin's transcriptional activity, whereas the expression of PIC increases it. Notably, this increase required the phosphatase activity of PIC. Thus, both isoforms have acquired opposing roles in the regulation of beta-catenin signaling. We also found that RPTPmu, another MAM family member, undergoes gamma-secretase-dependent processing. Our results identify intramembrane proteolysis as a regulatory switch in RPTPkappa signaling and implicate PIC in the activation of beta-catenin-mediated transcription.
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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.