ArticleMolecular and cellular biology2007
CSK controls retinoic acid receptor (RAR) signaling: a RAR-c-SRC signaling axis is required for neuritogenic differentiation.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- The role of RARG in solid tumor progression and therapeutic potential.Discover oncology · 2026Review
- Synthetic Retinoids for the Modulation of Genomic and Nongenomic Processes in Neurodegenerative Diseases.ACS omega · 2025Article
- Oncogenic RARγ isoforms promote head and neck cancer proliferation through vinexin-β-mediated cell cycle acceleration and autocrine activation of EGFR signal.International journal of biological sciences · 2025Article
- Non-canonical retinoid signaling in neural development, regeneration and synaptic function.Frontiers in molecular neuroscience · 2024Review
- Deregulation of All-International journal of molecular sciences · 2023Review
- Targeting the Retinoic Acid Pathway to Eradicate Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Apoptosis regulation by the tyrosine-protein kinase CSK.Frontiers in cell and developmental biology · 2022Review
- Dynamics of vitamin A uptake, storage, and utilization in vocal fold mucosa.Molecular metabolism · 2020Article
- Unorthodox Transcriptional Mechanisms of Lipid-Sensing Nuclear Receptors in Macrophages: Are We Opening a New Chapter?Frontiers in endocrinology · 2020Review
- Genomic and non-genomic pathways are both crucial for peak induction of neurite outgrowth by retinoids.Cell communication and signaling : CCS · 2019Article
- RAC1 Takes the Lead in Solid Tumors.Cells · 2019Review
- Bexarotene - a novel modulator of AURKA and the primary cilium inJournal of cell science · 2018Article
- Rhythmic Diurnal Synthesis and Signaling of Retinoic Acid in the Rat Pineal Gland and Its Action to Rapidly Downregulate ERK Phosphorylation.Molecular neurobiology · 2018Article
- All-trans-retinoic acid activates the pro-invasive Src-YAP-Interleukin 6 axis in triple-negative MDA-MB-231 breast cancer cells while cerivastatin reverses this action.Scientific reports · 2018Article
- Genetic and pharmacological inhibition of retinoic acid receptor γ function promotes endochondral bone formation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017Article
- Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma.Scientific reports · 2017Article
- Retinoids and rexinoids in cancer prevention: from laboratory to clinic.Seminars in oncology · 2016Review
- All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.PloS one · 2015Article
- All-Trans Retinoic Acid Induces Proliferation, Survival, and Migration in A549 Lung Cancer Cells by Activating the ERK Signaling Pathway through a Transcription-Independent Mechanism.BioMed research international · 2015Article
- The rhythm of retinoids in the brain.Journal of neurochemistry · 2014Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Herein, we report the first evidence that c-SRC is required for retinoic acid (RA) receptor (RAR) signaling, an observation that suggests a new paradigm for this family of nuclear hormone receptors. We observed that CSK negatively regulates RAR functions required for neuritogenic differentiation. CSK overexpression inhibited RA-mediated neurite outgrowth, a result which correlated with the inhibition of the SFK c-SRC. Consistent with an extranuclear effect of CSK on RAR signaling and neurite outgrowth, CSK overexpression blocked the downstream activation of RAC1. The conversion of GDP-RAC1 to GTP-RAC1 parallels the activation of c-SRC as early as 15 min following all-trans-retinoic acid treatment in LA-N-5 cells. The cytoplasmic colocalization of c-SRC and RARgamma was confirmed by immunofluorescence staining and confocal microscopy. A direct and ligand-dependent binding of RAR with SRC was observed by surface plasmon resonance, and coimmunoprecipitation studies confirmed the in vivo binding of RARgamma to c-SRC. Deletion of a proline-rich domain within RARgamma abrogated this interaction in vivo. CSK blocked the RAR-RA-dependent activation of SRC and neurite outgrowth in LA-N-5 cells. The results suggest that transcriptional signaling events mediated by RA-RAR are necessary but not sufficient to mediate complex differentiation in neuronal cells. We have elucidated a nongenomic extranuclear signal mediated by the RAR-SRC interaction that is negatively regulated by CSK and is required for RA-induced neuronal differentiation.
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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.