ArticleProceedings of the National Academy of Sciences of the United States of America2014
Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 39 citations in OpenAlex.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Review
- PHLPP1 regulates region-specific astroglial mitochondrial fission in response to oxidative stress in the male rat hippocampus.Scientific reports · 2025Article
- Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.Bone · 2024Article
- Characterizing crosstalk in epigenetic signaling to understand disease physiology.The Biochemical journal · 2023Article
- Emerging roles of PHLPP phosphatases in lung cancer.Frontiers in oncology · 2023Review
- PHLPP Signaling in Immune Cells.Current topics in microbiology and immunology · 2022Review
- On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart.Cellular signalling · 2021Review
- Myeloid Lineage Ablation ofInternational journal of molecular sciences · 2021Article
- Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.Osteoarthritis and cartilage open · 2021Article
- Emerging roles of PHLPP phosphatases in metabolism.BMB reports · 2021Review
- Pleckstrin homology (PH) domain and Leucine Rich Repeat Phosphatase 1 (Phlpp1) Suppresses Parathyroid Hormone Receptor 1 (Pth1r) Expression and Signaling During Bone Growth.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- PHLPPing the balance: restoration of protein kinase C in cancer.The Biochemical journal · 2021Review
- PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling.Annual review of pharmacology and toxicology · 2021Review
- PHLPP2 as a novel metastatic and prognostic biomarker in non-small cell lung cancer patients.Thoracic cancer · 2019Article
- Myosin 1b Regulates Nuclear AKT Activation by Preventing Localization of PTEN in the Nucleus.iScience · 2019Article
- Article
- Deficiency in the phosphatase PHLPP1 suppresses osteoclast-mediated bone resorption and enhances bone formation in mice.The Journal of biological chemistry · 2019Article
- Protein phosphatases in chromatin structure and function.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Enhanced Neutrophil Immune Homeostasis Due to Deletion of PHLPP.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Growth factor receptor levels are aberrantly high in diverse cancers, driving the proliferation and survival of tumor cells. Understanding the molecular basis for this aberrant elevation has profound clinical implications. Here we show that the pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) suppresses receptor tyrosine kinase (RTK) signaling output by a previously unidentified epigenetic mechanism unrelated to its previously described function as the hydrophobic motif phosphatase for the protein kinase AKT, protein kinase C, and S6 kinase. Specifically, we show that nuclear-localized PHLPP suppresses histone phosphorylation and acetylation, in turn suppressing the transcription of diverse growth factor receptors, including the EGF receptor. These data uncover a much broader role for PHLPP in regulation of growth factor signaling beyond its direct inactivation of AKT: By suppressing RTK levels, PHLPP dampens the downstream signaling output of two major oncogenic pathways, the PI3 kinase/AKT and the Rat sarcoma (RAS)/ERK pathways. Our data are consistent with a model in which PHLPP modifies the histone code to control the transcription of RTKs.
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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.