ArticleNature communications2018
The orphan GPR50 receptor promotes constitutive TGFβ receptor signaling and protects against cancer development.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Structure of the melatonin-related orphan receptor, GPR50.Molecules and cells · 2026Article
- Crosstalk of NPY and TGFβ orchestrates the signaling to facilitate perineural invasion of oral squamous cell carcinoma.British journal of cancer · 2026Article
- Repetitive transcranial magnetic stimulation alleviates neuropathic pain via microglial polarization by modulating the METTL3/NMDAR2B/NLRP3 pathway.Frontiers in immunology · 2025Article
- High expression of GPR50 promotes the proliferation, migration and autophagy of hepatocellular carcinoma cells in vitro.Journal of cell communication and signaling · 2023Article
- Advanced 3D dynamic culture system with transforming growth factor-β3 enhances production of potent extracellular vesicles with modified protein cargoes via upregulation of TGF-β signaling.Journal of advanced research · 2023Article
- Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.Cell chemical biology · 2023Article
- The Orphan GPR50 Receptor Regulates the Aggressiveness of Breast Cancer Stem-like Cells via Targeting the NF-kB Signaling Pathway.International journal of molecular sciences · 2023Article
- Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2022Article
- An Improved Genetically Encoded Fluorescent cAMP Indicator for Sensitive cAMP Imaging and Fast Drug Screening.Frontiers in pharmacology · 2022Article
- GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1.Nature communications · 2021Article
- The role of TGF-β2 in cartilage development and diseases.Bone & joint research · 2021Article
- Specification and epigenomic resetting of the pig germline exhibit conservation with the human lineage.Cell reports · 2021Article
- GPR50-Ctail cleavage and nuclear translocation: a new signal transduction mode for G protein-coupled receptors.Cellular and molecular life sciences : CMLS · 2020Article
- GPR50 Promotes Hepatocellular Carcinoma Progression via the Notch Signaling Pathway through Direct Interaction with ADAM17.Molecular therapy oncolytics · 2020Article
- Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain.Journal of pain research · 2020Article
- Molecular identification of a BAR domain-containing coat complex for endosomal recycling of transmembrane proteins.Nature cell biology · 2019Article
- GPR50 in TGFβ signaling and breast cancer.Oncoscience · 2018Article
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGFβ) signaling is initiated by the type I, II TGFβ receptor (TβRI/TβRII) complex. Here we report the formation of an alternative complex between TβRI and the orphan GPR50, belonging to the G protein-coupled receptor super-family. The interaction of GPR50 with TβRI induces spontaneous TβRI-dependent Smad and non-Smad signaling by stabilizing the active TβRI conformation and competing for the binding of the negative regulator FKBP12 to TβRI. GPR50 overexpression in MDA-MB-231 cells mimics the anti-proliferative effect of TβRI and decreases tumor growth in a xenograft mouse model. Inversely, targeted deletion of GPR50 in the MMTV/Neu spontaneous mammary cancer model shows decreased survival after tumor onset and increased tumor growth. Low GPR50 expression is associated with poor survival prognosis in human breast cancer irrespective of the breast cancer subtype. This describes a previously unappreciated spontaneous TGFβ-independent activation mode of TβRI and identifies GPR50 as a TβRI co-receptor with potential impact on cancer development.
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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.