ArticleNature cell biology2012
PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12.
Article in Nature cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Integrative meta-analysis of differentially expressed genes in osteoarthritis using microarray technology.Molecular medicine reports · 2015Pooled it
- Targeting chemotherapy resistance in mesenchymal triple-negative breast cancer: a phase II trial of neoadjuvant angiogenic and mTOR inhibition with chemotherapy.Investigational new drugs · 2023Trial
- Targeting mTOR in Systemic Lupus Erythematosus: From Immune Cell Dysfunction to Clinical Translation.Journal of inflammation research · 2026Review
- Review
- Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2.Journal of cell science · 2025Article
- Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer.Oncogene · 2025Article
- Genetic Insights into Brain Morphology: a Genome-Wide Association Study of Cortical Thickness and TNeuroinformatics · 2025Article
- Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody.Nature medicine · 2025Article
- Cross-modal contrastive learning decodes developmental regulatory features through chromatin potential analysis.GigaScience · 2025Article
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- PKC-δ Promotes IL-1β-Induced Apoptosis of Rat Chondrocytes and Via Activating JNK and P38 MAPK Pathways.Cartilage · 2024Article
- GRespiratory research · 2024Review
- E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (IThe Journal of biological chemistry · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Comprehensive considerations for dermatologists: the application of FDG-PET in evaluating cutaneous lesions in pediatric Langerhans cell histiocytosis.Frontiers in medicine · 2024Review
- Somatic ARAF mutations in pediatric Langerhans cell histiocytosis: clinicopathologic, genetic and functional profiling.Clinical and experimental medicine · 2023Article
- UsingCells · 2023Review
- Endometriosis-Associated Ovarian Carcinomas: How PI3K/AKT/mTOR Pathway Affects Their Pathogenesis.Biomolecules · 2023Review
- ETS-1-activated LINC01016 over-expression promotes tumor progression via suppression of RFFL-mediated DHX9 ubiquitination degradation in breast cancers.Cell death & disease · 2023Article
- Characterization of genome-wide STR variation in 6487 human genomes.Nature communications · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates AGC protein kinases including protein kinase C (PKC) and regulates cellular functions such as cell migration. However, its regulation remains poorly understood. Here we show that lysophosphatidic acid (LPA) induces two phases of PKC-δ hydrophobic motif phosphorylation. The late phase is mediated by Gα(12), which specifically activates ARAF, leading to upregulation of the RFFL E3 ubiquitin ligase and subsequent ubiquitylation and degradation of the PRR5L subunit of mTORC2. Destabilization of PRR5L, a suppressor of mTORC2-mediated hydrophobic motif phosphorylation of PKC-δ, but not AKT, results in PKC-δ hydrophobic motif phosphorylation and activation. This Gα(12)-mediated signalling pathway for mTORC2 regulation is critically important for fibroblast migration and pulmonary fibrosis development.
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.